Abstract: The present invention provides: a kit or device for detecting an ovarian tumor, the kit or device including a nucleic acid for detecting miRNA in a specimen from a subject; and a method for detecting an ovarian tumor, the method including the measurement of this miRNA in vitro.
Entitled kit for the detection of ovarian tumor, devices and methods
Technical field
[0001]
The present invention is used for inspection of the presence or absence of onset of ovarian tumors in a subject, specific miRNA, or a kit or device for the detection of ovarian tumor including its complementary strand capable of specifically binding a nucleic acid, and a method for detecting ovarian tumors comprising measuring the expression level of the miRNA with the nucleic acid.
BACKGROUND
[0002]
Ovary is one-by-one present on both sides of the uterus in the female-specific reproductive organs that produce eggs. Tubal the eggs released from the ovary is a tube before moving into the uterus, where the fertilized egg to grow and to implantation to the fetus. The ovary also has a function to secrete estrogen and progesterone is a female hormone. Ovary is the organ tumor is likely to occur, ovarian tumors from its generation origin, surface epithelial-stromal tumors, sex cord stromal tumors are broadly classified into germ cell tumors. Ovarian tumors are classified according to grade benign, borderline malignancy, malignant, ovarian tumors boundary malignant and malignant called ovarian cancer. Ovarian cancer incidence in Japan by the National Research and Development Institute of the National Cancer Research Center for Cancer Control and Information Center to disclose the 9,384 people in 2012, that is affected is one in 87 people Japanese women, ovarian cancer the number of deaths climb to 4,840 people in 2014. In the United States, a woman is said to be developing ovarian cancer by one person out of every 75 people, estimated ovarian cancer sufferers number of 2017 climbed to 22,440 people, of which about 14,080 people There is to die.
[0003]
Progression of ovarian cancer and fallopian tube cancer, tumors or unilateral or bilateral, is determined by the presence or absence and size of intraperitoneal dissemination, lymph node metastasis and distant metastasis, stage IA, IB, IC (IC1, IC2, IC3), IIA, IIB, IIIA1, IIIA2, IIIB, IIIC, IVA, is staging the IVB. 5-year relative survival rate for ovarian cancer is largely dependent on the progression of cancer, 92% if the cancer is localized, 73% if there is cancer in the peripheral region, distant metastasis cancer where permitted has been reported to be 29%. Therefore, finding the ovarian cancer at an early stage lead to improved survival, it provides means for allowing early detection have been required strongly.
[0004]
Although treatment of ovarian cancer in principle is a surgical therapy, progression and metastasis, general condition, medication is used in combination with classification of ovarian cancer. Especially if it is found as early ovarian cancer of stage I, uterus, ovary, rather than the total removal of the fallopian tube, there is a possibility that requires only surgery to remove only the ovary and fallopian tube cancer is found side, women it is possible to maintain the possibility of subsequent birth.
[0005]
In addition, early ovarian cancer and benign ovarian tumors are often there are no symptoms, and because it often does not occur only common symptoms even in advanced ovarian cancer can also occur in other causes, such as bloating and pain in the abdomen , it is difficult to find the ovarian tumor from subjective symptoms. Although the screening test for ovarian cancer have been made many studies, significant results have not been obtained, a method that can be actually used as inspection, transvaginal ultrasonography and blood marker CA-125 2 inspection It is the only one. The secondary examination of ovarian cancer, ultrasonography, CT scan test, MRI, there is an image tests, such as PET / CT.
[0006]
That albeit at the research stage, as shown in Patent Documents 1 to 4 and Non-Patent Documents 1-3, the expression level of a micro RNA in a biological sample, including blood (miRNA), to detect ovarian cancer report there is.
[0007]
Specifically, miR-191 of Patent Document 1 in plasma, miR-24, miR-320, miR-328, miR-625-3p, miR-483-5p, miR-92a, and miR-1290 method of predicting how and prognosis for detecting ovarian cancer using are shown.
[0008]
Patent Document 2 such miR-135a-3 in the blood is shown as a biomarker of gynecological cancer.
[0009]
Patent Document 3 using a human sample tissue miR-125a-3p, such as miR-211-3 is shown as a biomarker for ovarian cancer.
[0010]
In plasma in Patent Document 4 miR-191-5p, miR-652-5p, miR-744-5p, endometriosis by using a miR-1246 and endometriosis-derived ovarian cancer or ovarian serous how to determine the cancer is shown.
[0011]
miR-92a in the blood in non-patent document 1 as a circulating extracellular miRNA involved in ovarian cancer, miR-128, miR-191-5p, miR-296-5p, miR-320a, such as miR-625-3p is It is shown.
[0012]
The non-patent document 2 it is shown that there is a difference in expression level of such miR-22, miR-45 as the result of the analysis of ovarian cancer and benign disease patients and healthy individuals the serum specimens from miRNA in the next generation sequencers there.
[0013]
Non-Patent Document 3 miR-23a / b, there miR-92, miR-125a, miR-296-5p, miR-320, miR-422a, such as miR-663a is in fluid endoplasmic reticulum of ovarian cancer patients It has been shown to.
[0014]
Non-patent Document 4 sensitivity 77.4% to detect ovarian cancer blood marker CA-125, and specificity has been reported as 70.8%.
CITATION
Patent Document
[0015]
Patent Document 1: U.S. Patent Application Publication No. 2016/0312301 specification
Patent Document 2: JP 2010-154843 Patent Publication
Patent Document 3: JP-T 2010-538610 Patent Publication
Patent Document 4: WO 2013/148151
Non-patent literature
[0016]
Non-Patent Document 1: Nakamura K. Et al., 2016, Molelular Cancer. Volume 15, (1): 48
Non-Patent Document 2: Ji T. Et al., 2014, Asian Pacific Journal of Cancer Prevention. Vol. 15, (4): 1739
Non-Patent Document 3: Giusti I. Et al., 2013, BioMed Research International. The 2013 Volume, 703048
Non-Patent Document 4: Kim YW. Et al., 2012, PLoS One. Vol. 7, (9): e44960
Summary of the Invention
Problems that the Invention is to Solve
[0017]
An object of the present invention is to provide a method capable of effectively detecting the ovarian tumors with a nucleic acid to found a novel ovarian tumor marker, to detect the marker.
[0018]
That the symptoms find ovarian tumors are difficult and screening methods for ovarian tumors are only two transvaginal ultrasonography and tumor marker CA-125 test. However, transvaginal ultrasonography is able to detect the tumor by using ultrasonic waves from intravaginally, have a limited range of ultrasonic arrives, it may not be found a tumor which exists away from the vagina. Furthermore, CA-125 is a protein in the blood, but are said to be increased in ovarian cancer patients, often towards increasing for different reasons and ovarian tumor, whereas even ovarian tumors CA- since 125 levels some patients do not increase, CA-125 test is not a valid screening test. Further, as described above, according to non-patent document 4, the sensitivity for detecting ovarian cancer CA-125 77.4% and specificity is reported to 70.8%.
[0019]
Further, transvaginal ultrasonography, be carried out tumor marker CA-125 test is found that does not lead to a decrease in the mortality rate of ovarian cancer.
[0020]
Although reports that although the research stage to determine the ovarian tumors with the expression level of miRNA in a biological sample, including blood is as follows, neither put to practical use.
[0021]
miR-191 in plasma in Patent Document 1, miR-24, miR-320, miR-328, miR-625-3p, miR-483-5p, miR-92a, using the miRNA, such as miR-1290 ovary a method of predicting how and prognosis of detecting cancer are shown, these miRNA are not suitable for the method for detecting the presence or absence of ovarian cancer is also expressed in the control group. The number of specimens was also performed unreliable tens cases and less marker.
[0022]
Although the patent document 2 miRNA, such as miR-135a-3 in the blood is shown as a biomarker of gynecological cancer, it has been shown only miRNA expression differences regarding endometrial cancer, determination of ovarian cancer specific accuracy of sensitivity, there is no description about the detection performance such as specificity, poor industrial practicality.
[0023]
Patent Document 3 using a human sample tissue miR-125a-3p, although miRNA such as miR-211-3 is shown as a biomarker for ovarian cancer, the availability of tissue specimens tissue ablation surgical is essential, this step is heavier is physical burden on the patient, it is not preferable as an inspection method. Further, specific precision for determining ovarian cancer, sensitivity, there is no description about the detection performance such as specificity, poor industrial practicality.
[0024]
miR-191-5p in plasma in Patent Document 4, miR-652-5p, miR-744-5p, ovary cancer or serous endometriosis and endometriosis using a miRNA such as miR-1246 a method of determining the sex ovarian cancer are shown, because the discrimination between ovarian cancer and other cancers are not shown, a risk that was detected as ovarian cancer accidentally other cancers there is. Further, also the number of specimens was also performed unreliable tens cases and less marker.
[0025]
miR-92a in the blood in non-patent document 1 as a circulating extracellular miRNA involved in ovarian cancer, miR-128, miR-191-5p, miR-296-5p, miR-320a, such as miR-625-3p is It is shown. However, the detection sensitivity of ovarian epithelial cancer by the combination of miR-205 and the let-7f low 62.4% missed ovarian cancer is concerned. In addition, it has been shown other miRNA The combined ovarian cancer and healthy individuals of discrimination performance is also part, because it does not incorporate a patient of other cancers in the study, the other cancer and ovarian cancer erroneous There is a risk that in another, undesirable lead to a delay of unnecessary additional tests and of the original cancer detection.
[0026]
It is the non-patent document 2 there is a difference between the expression level of miRNA, such as miR-22, miR-45 as the result of the analysis of ovarian cancer and benign disease patients and healthy individuals the serum specimens from miRNA in the next generation sequencers are shown have been, concrete precision for determining ovarian cancer, sensitivity, there is no description about the detection performance such as specificity, poor industrial practicality.
[0027]
Non-Patent Document 3 miR-23a / b, miR-92, miR-125a, miR-296-5p, miR-320, miR-422a, miRNA, such as miR-663a is in fluid endoplasmic reticulum of ovarian cancer patients have been shown to be present in the specific accuracy for determining ovarian cancer, sensitivity, there is no description about the detection performance such as specificity, poor industrial practicality.
[0028]
Thus, in the detection of ovarian tumors, because existing tumor markers its performance is low and the method of performance and detection for marker research stage are not shown specifically, in the case of using them, the healthy subjects performed and wasteful additional testing by detecting erroneously ovarian tumor patients, there is a possibility that loss occurs therapeutic opportunities due to overlook the ovarian tumor patients. Also, taking a ovarian tissue in order to measure the tumor marker is highly undesirable invasive to the patient. Therefore, can be detected from the blood can be collected in a minimally invasive, and ovarian tumor patients ovarian tumor patients, healthy subjects correctly determined that a healthy person, there is a demand high ovarian cancer markers accurate. In particular, ovarian cancer by discovered early treatment, to maintain the potential for dramatically to can be reduced, also partial subsequent birth if STOP resection surgery women recurrence risk because it can, high ovarian cancer markers sensitive to detect even low ovarian cancer of progress has been desired. Further, by providing a more convenient ovarian tumor primary screening test, may lead to improvement in the consultation rate of the secondary inspection is envisaged.
Means for Solving the Problems
[0029]
The present inventors have result of intensive studies to solve the above problems, the blood can be collected in less invasive discovered micro RNA (miRNA) gene markers that can be used as a detection marker for ovarian tumors, nucleic acids for the detection of this marker , for example by using at least one or at least two nucleic acid selected from the primers that amplify the probe and the marker capable of specifically binding the marker, significantly ovarian tumors, it preferably specifically, can be detected the finding has led to the completion of the present invention.
[0030]
In other words, the present invention has the following characteristics.
(1) ovarian tumor marker, miR-4675, miR-4783-3p , miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307 -3p, miR-8073, miR- 3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p , miR-4730, miR-6885-5p , miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, miR-1260b, miR-4258, miR-4697-5p, miR -1469, miR-4515, miR- 6861 5p, miR-6821-5p, miR- 575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885- 3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749- 5p, miR-6729-5p, miR- 6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a- 5p, miR-6816-5p, miR- 296-3p, mi -7977, miR-8069, miR- 6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR-614 , miR-4689, miR-1185-2-3p , miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR-1275 , miR-5001-5p, miR-6826-5p , miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR -6766-3p, miR-197-5p, miR- 68 87-5p, miR-6742-5p, miR- 6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR-6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR- 6840-3p, miR-4476, miR- 675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR-3648, miR-4732-5p, miR 4787-5p, miR-3917, miR- 619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR- 6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR- 4435, miR-4747-3p, miR- 6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p, miR-4433a-3p, miR- 4274, m R-4419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR- 4736, miR-718, miR- 6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR-6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722- 5p, miR-4746-3p, miR- 4450, mi R-6795-5p, miR-365a- 5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR-6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671- 5p, miR-4667-5p, miR- 4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR- 6763-5p, miR-1908-3p, miR- 1181, iR-6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR- 4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR- 3141, miR-3162-5p, miR- 4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR-6791-5p, miR-681 -5p, miR-6891-5p, miR- 7108-5p, miR-7109-5p, a complementary strand of at least one polynucleotide or said polynucleotide selected from the miR-642b-3p and miR-642a-3p specifically includes binding nucleic acid detection kit for ovarian tumors.
[0031]
(2) miR-4675 is hsa-miR-4675, miR- 4783-3p is hsa-miR-4783-3p, miR- 1228-5p is hsa-miR-1228-5p, miR- 4532 There is a hsa-miR-4532, miR- 6802-5p is hsa-miR-6802-5p, miR- 6784-5p is hsa-miR-6784-5p, miR- 3940-5p is hsa-miR is a -3940-5p, miR-1307-3p is hsa-miR-1307-3p, miR- 8073 is hsa-miR-8073, miR- 3184-5p is located in hsa-miR-3184-5p , miR-1233-5p is hsa-miR-1233-5p, miR- 608 There is a hsa-miR-6088, miR- 5195-3p is hsa-miR-5195-3p, miR- 320b is hsa-miR-320b, miR- 4649-5p is hsa-miR-4649-5p in it, miR-6800-5p is hsa-miR-6800-5p, miR- 1343-3p is hsa-miR-1343-3p, miR- 4730 is hsa-miR-4730, miR- 6885 -5p is hsa-miR-6885-5p, miR- 5100 is hsa-miR-5100, miR- 1203 is hsa-miR-1203, miR- 6756-5p is hsa-miR-6756-5p in it, miR-373-5p is hsa-miR-373-5p, iR-1268a is hsa-miR-1268a, miR- 1260b is hsa-miR-1260b, miR- 4258 is hsa-miR-4258, miR- 4697-5p is in hsa-miR-4697-5p Yes, miR-1469 is hsa-miR-1469, miR- 4515 is hsa-miR-4515, miR- 6861-5p is hsa-miR-6861-5p, is miR-6821-5p hsa- is a miR-6821-5p, miR-575 is hsa-miR-575, miR- 6805-5p is hsa-miR-6805-5p, miR- 4758-5p is in hsa-miR-4758-5p Yes, miR-3663-3p is hsa-miR-3663-3p In it, miR-4530 is hsa-miR-4530, miR- 6798-5p is hsa-miR-6798-5p, miR- 6781-5p is hsa-miR-6781-5p, miR- 885 -3p is hsa-miR-885-3p, miR- 1273g-3p is hsa-miR-1273g-3p, miR-4787-3p is hsa-miR-4787-3p, is miR-4454 hsa is a -miR-4454, miR-4706 is hsa-miR-4706, miR- 1249-3p is hsa-miR-1249-3p, miR- 887-3p is located in hsa-miR-887-3p , miR-6786-5p is hsa-miR-6786-5p, miR- 1238 5p is hsa-miR-1238-5p, miR- 6749-5p is hsa-miR-6749-5p, miR- 6729-5p is hsa-miR-6729-5p, is miR-6825-5p is hsa-miR-6825-5p, miR- 663b is hsa-miR-663b, miR- 6858-5p is hsa-miR-6858-5p, miR- 4690-5p is hsa-miR-4690- is 5p, miR-6765-5p is hsa-miR-6765-5p, miR- 4710 is hsa-miR-4710, miR- 6775-5p is hsa-miR-6775-5p, miR- 371a-5p is hsa-miR-371a-5p, is miR-6816-5p is a sa-miR-6816-5p, miR- 296-3p is hsa-miR-296-3p, miR- 7977 is hsa-miR-7977, miR- 8069 is hsa-miR-8069, miR-6515-3p is hsa-miR-6515-3p, miR- 4687-5p is hsa-miR-4687-5p, miR- 1343-5p is hsa-miR-1343-5p, miR- 7110-5p is hsa-miR-7110-5p, miR- 4525 is hsa-miR-4525, miR- 3158-5p is hsa-miR-3158-5p, is miR-6787-5p hsa- It is a miR-6787-5p, miR-614 is hsa-miR-614, mi R-4689 is hsa-miR-4689, miR- 1185-2-3p is hsa-miR-1185-2-3p, miR- 1268b is hsa-miR-1268b, the miR-1228-3p a hsa-miR-1228-3p, miR- 1185-1-3p is hsa-miR-1185-1-3p, miR- 940 is hsa-miR-940, is miR-939-5p hsa- is a miR-939-5p, miR-6757-5p is hsa-miR-6757-5p, miR- 1275 is hsa-miR-1275, miR- 5001-5p is in hsa-miR-5001-5p Yes, miR-6826-5p is hsa-miR-6826-5p, is miR-6765-3p is a sa-miR-6765-3p, miR- 3679-3p is hsa-miR-3679-3p, miR- 4718 is hsa-miR-4718, miR- 4286 is hsa-miR-4286, miR-8059 is hsa-miR-8059, miR- 4447 is hsa-miR-4447, miR- 4448 is hsa-miR-4448, miR- 658 is hsa-miR-658, miR- 6766-3p is hsa-miR-6766-3p, miR- 197-5p is hsa-miR-197-5p, miR- 6887-5p is hsa-miR-6887-5p, miR- 6742- 5p is hsa-miR-6742-5p, miR- 6729-3p is h is a a-miR-6729-3p, miR- 5090 is hsa-miR-5090, miR- 7975 is hsa-miR-7975, miR- 4505 is hsa-miR-4505, miR- 6889- 5p is hsa-miR-6889-5p, miR- 4708-3p is hsa-miR-4708-3p, miR- 6131 is hsa-miR-6131, miR- 1225-3p is hsa-miR- is a 1225-3p, miR-6132 is hsa-miR-6132, miR- 4734 is hsa-miR-4734, miR- 3194-3p is hsa-miR-3194-3p, miR- 638 is is hsa-miR-638, miR- 2467-3p is hsa-miR Is a -2467-3p, miR-4728-5p is hsa-miR-4728-5p, miR- 5572 is hsa-miR-5572, miR- 6789-5p is located in hsa-miR-6789-5p , miR-8063 is hsa-miR-8063, miR- 4429 is hsa-miR-4429, miR- 6840-3p is hsa-miR-6840-3p, miR- 4476 is hsa-miR-4476 in and, miR-675-5p is hsa-miR-675-5p, miR- 711 is hsa-miR-711, miR- 6875-5p is hsa-miR-6875-5p, miR- 3160 -5p is hsa-miR-3160-5p, miR- 1908-5p is hs Is a -miR-1908-5p, miR-6726-5p is hsa-miR-6726-5p, miR- 1913 is hsa-miR-1913, miR- 8071 is hsa-miR-8071, miR -3648 is hsa-miR-3648, miR- 4732-5p is hsa-miR-4732-5p, miR- 4787-5p is hsa-miR-4787-5p, miR- 3917 is hsa-miR is -3917, miR-619-5p is hsa-miR-619-5p, miR- 1231 is hsa-miR-1231, miR- 342-5p is hsa-miR-342-5p, miR -4433a-5p is hsa-miR-4433a-5p, miR-676 -5p is hsa-miR-6766-5p, miR- 4707-5p is hsa-miR-4707-5p, miR- 7114-5p is hsa-miR-7114-5p, miR- 6872-3p There is a hsa-miR-6872-3p, miR- 6780b-5p is hsa-miR-6780b-5p, miR-7845-5p is hsa-miR-7845-5p, miR- 6798-3p is hsa -miR-6798-3p is, miR-665 is hsa-miR-665, miR- 6848-5p is hsa-miR-6848-5p, miR- 5008-5p is hsa-miR-5008-5p in it, miR-4294 is hsa-miR-4294, miR- 6511a-5p There is a hsa-miR-6511a-5p, miR-4435 is hsa-miR-4435, miR- 4747-3p is hsa-miR-4747-3p, miR- 6880-3p is hsa-miR-6880 is a -3p, miR-6869-5p is hsa-miR-6869-5p, miR- 7150 is hsa-miR-7150, miR- 1260a is hsa-miR-1260a, miR- 6877-5p There is a hsa-miR-6877-5p, miR- 6721-5p is hsa-miR-6721-5p, miR- 4656 is hsa-miR-4656, miR- 1229-5p is hsa-miR-1229 is a -5p, miR-4433a-3p is hsa-miR-443 is a a-3p, miR-4274 is hsa-miR-4274, miR- 4419b is hsa-miR-4419b, miR- 4674 is hsa-miR-4674, is miR-6893-5p hsa- is a miR-6893-5p, miR-6763-3p is hsa-miR-6763-3p, miR- 6762-5p is hsa-miR-6762-5p, miR- 6738-5p is hsa-miR- is a 6738-5p, miR-4513 is hsa-miR-4513, miR- 6746-5p is hsa-miR-6746-5p, miR- 6880-5p is hsa-miR-6880-5p, miR-4736 is hsa-miR-4736, miR- 718 is hsa is a miR-718, miR-6717-5p is hsa-miR-6717-5p, miR- 7847-3p is hsa-miR-7847-3p, miR- 760 is hsa-miR-760, miR-1199-5p is hsa-miR-1199-5p, miR- 6813-5p is hsa-miR-6813-5p, miR- 6769a-5p is hsa-miR-6769a-5p, miR- 1193 is hsa-miR-1193, miR- 7108-3p is hsa-miR-7108-3p, miR- 6741-5p is hsa-miR-6741-5p, miR- 4298 is hsa-miR- is 4298, miR-6796-3p is located in hsa-miR-6796-3p , MiR-4750-5p is hsa-miR-4750-5p, miR- 6785-5p is hsa-miR-6785-5p, miR- 1292-3p is hsa-miR-1292-3p, miR -4749-3p is hsa-miR-4749-3p
is, miR-6800-3p is hsa-miR-6800-3p, miR- 722-5p is hsa-miR-4722-5p, miR- 4746 -3p is hsa-miR-4746-3p, miR- 4450 is hsa-miR-4450, miR- 6795-5p is hsa-miR-6795-5p, miR- 365a-5p is hsa-miR is a -365a-5p, miR-498 is hsa-miR-498, miR- 67 7-5p is hsa-miR-6797-5p, miR- 1470 is hsa-miR-1470, miR- 6851-5p is hsa-miR-6851-5p, is miR-1247-3p hsa- is a miR-1247-3p, miR-5196-5p is hsa-miR-5196-5p, miR- 208a-5p is hsa-miR-208a-5p, miR-6842-5p is hsa-miR- is a 6842-5p, miR-150-3p is hsa-miR-150-3p, miR- 4534 is hsa-miR-4534, miR- 3135b is hsa-miR-3135b, is miR-3131 is hsa-miR-3131, miR- 4792 is in hsa-miR-4792 Ri, miR-6510-5p is hsa-miR-6510-5p, miR- 504-3p is hsa-miR-504-3p, miR- 3619-3p is hsa-miR-3619-3p, miR-671-5p is hsa-miR-671-5p, miR- 4667-5p is hsa-miR-4667-5p, miR- 4430 is hsa-miR-4430, miR- 3195 is hsa- is a miR-3195, miR-3679-5p is hsa-miR-3679-5p, miR- 6076 is hsa-miR-6076, miR- 6515-5p is hsa-miR-6515-5p, miR-6820-5p is hsa-miR-6820-5p, miR- 4634 is hsa Is a -miR-4634, miR-187-5p is hsa-miR-187-5p, miR- 6763-5p is hsa-miR-6763-5p, miR- 1908-3p is hsa-miR-1908 is a -3p, miR-1181 is hsa-miR-1181, miR- 6782-5p is hsa-miR-6782-5p, miR- 5010-5p is hsa-miR-5010-5p, miR -6870-5p is hsa-miR-6870-5p, miR- 6124 is hsa-miR-6124, miR- 1249-5p is hsa-miR-1249-5p, miR- 6511b-5p is hsa is a -miR-6511b-5p, miR- 1254 is in hsa-miR-1254 Ri, miR-4727-3p is hsa-miR-4727-3p, miR- 4259 is hsa-miR-4259, miR- 4771 is hsa-miR-4771, is miR-3622a-5p hsa- is a miR-3622a-5p, miR- 4480 is hsa-miR-4480, miR- 4740-5p is hsa-miR-4740-5p, miR- 6777-5p is in hsa-miR-6777-5p Yes, miR-6794-5p is hsa-miR-6794-5p, miR- 4687-3p is hsa-miR-4687-3p, miR- 6743-5p is hsa-miR-6743-5p, miR-6771-5p is hsa-miR-6771-5p, miR- 3 41 is hsa-miR-3141, miR- 3162-5p is hsa-miR-3162-5p, miR- 4271 is hsa-miR-4271, miR- 1227-5p is hsa-miR-1227- is 5p, miR-4257 is hsa-miR-4257, miR- 4270 is hsa-miR-4270, miR- 4516 is hsa-miR-4516, miR- 4651 is in hsa-miR-4651 Yes, miR-4725-3p is hsa-miR-4725-3p, miR- 6125 is hsa-miR-6125, miR- 6732-5p is hsa-miR-6732-5p, miR- 6791- 5p is hsa-miR-6791-5p, miR- 6819- 5p is hsa-miR-6819-5p, miR- 6891-5p is hsa-miR-6891-5p, miR- 7108-5p is hsa-miR-7108-5p, is miR-7109-5p a hsa-miR-7109-5p, miR- 642b-3p is hsa-miR-642b-3p, miR-642a-3p is hsa-miR-642a-3p, kit according to (1).
[0032]
(3) the nucleic acid, polynucleotide in any of the following (a) -
(e): (a) in the nucleotide sequence or the nucleotide sequence shown in any of SEQ ID NO: 1 to 247,251 and 268 polynucleotides, a variant thereof u is the nucleotide sequence is t, a derivative thereof, or a fragment thereof comprising 15 or more continuous
nucleotides, represented by any one of (b) SEQ ID NO: 1 to 247,251 and 268 polynucleotide comprising a nucleotide sequence,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (c) SEQ ID NO: 1 to 247,251 and 268 , a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous
nucleotides, represented by any one of (d) SEQ ID NO: 1 to 247,251 and 268 That nucleotide sequence or polynucleotide u in the nucleotide sequence comprises a nucleotide sequence complementary to the nucleotide sequence is t, and
(e) above (a) in any of the polynucleotides under stringent conditions of ~ (d) hybridizing polynucleotide,
a polynucleotide selected from the group consisting of the kit according to (1) or (2).
[0033]
(4) the kit is another ovarian tumor marker, miR-320a, miR-663a, miR-328-5p, miR-128-2-5p, miR-125a-3p, miR-191-5p, miR -92b-5p, miR-296-5p, miR-1246, miR-92a-2-5p, miR-128-1-5p, miR-1290, miR-211-3p, miR-744-5p, miR-135a -3p, miR-451a, miR-625-3p, miR-92a-3p, miR-422a, miR-483-5p, miR-652-5p, miR-24-3p, miR-23b-3p, miR-23a -3p, miR-92b-3p, at least one polynucleotide selected from miR-22-3p, or the poly Further comprising a complementary strand capable of specifically binding a nucleic acid of Kureochido kit according to any one of (1) to (3).
[0034]
(5) miR-320a is hsa-miR-320a, miR-663a is hsa-miR-663a, miR-328-5p is hsa-miR-328-5p, miR-128-2-5p There is a hsa-miR-128-2-5p, miR-125a-3p is hsa-miR-125a-3p, miR-191-5p is hsa-miR-191-5p, miR-92b-5p There is a hsa-miR-92b-5p, miR-296-5p is hsa-miR-296-5p, miR-1246 is hsa-miR-1246, miR-92a-2-5p is hsa-miR is a -92a-2-5p, miR-128-1-5p is hsa-miR-128-1-5p, is miR-1290 Is a sa-miR-1290, miR-211-3p is hsa-miR-211-3p, miR-744-5p is hsa-miR-744-5p, miR-135a-3p is hsa-miR- a 135a-3p, miR-451a is hsa-miR-451a, miR-625-3p is hsa-miR-625-3p, miR-92a-3p is hsa-miR-92a-3p, miR-422a is hsa-miR-422a, miR-483-5p is hsa-miR-483-5p, miR-652-5p is hsa-miR-652-5p, is miR-24-3p is hsa-miR-24-3p, miR-23b-3p is hsa-miR-23b-3p, miR-23 -3p is hsa-miR-23a-3p, miR-92b-3p is hsa-miR-92b-3p, miR-22-3p is hsa-miR-22-3p, according to (4) kit.
[0035]
(6) The nucleic acid polynucleotide in any of the following (f) -
(j): (f) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 nucleotide sequence or represented by any one of the ~ 275 the nucleotide u in sequence consisting of the nucleotide sequence is t polynucleotides, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous
nucleotides, (g) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ a polynucleotide comprising a nucleotide sequence represented by any one of
275, u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (h) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 polynucleotides, a variant thereof comprising a nucleotide sequence complementary to the nucleotide sequence, the fragment comprising the derivative, or 15 or more contiguous bases,
(I) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence shown in any of 275, and
( j) above (f) any of the polynucleotides under stringent conditions with a polynucleotide hybridizing of ~ (i),
a polynucleotide selected from the consisting of group, as described in (4) or (5) kit.
[0036]
(7) The kit of (1) or (2) at least two polynucleotides selected from all ovarian tumor markers described, or respectively capable of specifically binding at least two complementary strands of the polynucleotide one of containing a nucleic acid, the kit according to any one of (6) from (1).
[0037]
(8) 卵 巣 腫 瘍 マ ー カ ー で あ る, miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307 -3P, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p , miR-4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, 1260b-miR, miR-4258, miR-4697-5p, miR -1469, miR-4515, miR-6861 5p, miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885- 3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749- 5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a- 5p, miR-6816-5p, miR-296-3p, mi -7977, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR-614 , miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR-1275 , miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR -6766-3p, miR-197-5p, miR-68 87-5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR-6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR 6840-3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR-3648, miR-4732-5p, miR 4787-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR 6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR 4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p, miR-4433a-3p, miR-4274, m R-4419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR 4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR-6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722- 5p, miR-4746-3p, miR-4450, mi R-6795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR-6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671- 5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR 6763-5p, miR-1908-3p, miR-1181, iR 6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR 4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR 3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR-6791-5p, miR-681 -5p, miR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p 及 び miR-642a-3p か ら 選 択 さ れ る 少 な く と も 1 つ の ポ リ ヌ ク レ オ チ ド, 又 は 該 ポ リ ヌ ク レ オ チ ド の 相 補 鎖 と特異 的 に 結合 可能 な 核酸 を 含 む, 卵 巣 腫 瘍 の 検 出 用 デ バ イ ス.
[0038]
(9) miR-4675 is hsa-miR-4675, miR- 4783-3p is hsa-miR-4783-3p, miR- 1228-5p is hsa-miR-1228-5p, miR- 4532 There is a hsa-miR-4532, miR- 6802-5p is hsa-miR-6802-5p, miR- 6784-5p is hsa-miR-6784-5p, miR- 3940-5p is hsa-miR is a -3940-5p, miR-1307-3p is hsa-miR-1307-3p, miR- 8073 is hsa-miR-8073, miR- 3184-5p is located in hsa-miR-3184-5p , miR-1233-5p is hsa-miR-1233-5p, miR- 608 There is a hsa-miR-6088, miR- 5195-3p is hsa-miR-5195-3p, miR- 320b is hsa-miR-320b, miR- 4649-5p is hsa-miR-4649-5p in it, miR-6800-5p is hsa-miR-6800-5p, miR- 1343-3p is hsa-miR-1343-3p, miR- 4730 is hsa-miR-4730, miR- 6885 -5p is hsa-miR-6885-5p, miR- 5100 is hsa-miR-5100, miR- 1203 is hsa-miR-1203, miR- 6756-5p is hsa-miR-6756-5p in it, miR-373-5p is hsa-miR-373-5p, iR-1268a is hsa-miR-1268a, miR- 1260b is hsa-miR-1260b, miR- 4258 is hsa-miR-4258, miR- 4697-5p is in hsa-miR-4697-5p Yes, miR-1469 is hsa-miR-1469, miR- 4515 is hsa-miR-4515, miR- 6861-5p is hsa-miR-6861-5p, is miR-6821-5p hsa- is a miR-6821-5p, miR-575 is hsa-miR-575, miR- 6805-5p is hsa-miR-6805-5p, miR- 4758-5p is in hsa-miR-4758-5p Yes, miR-3663-3p is hsa-miR-3663-3p In it, miR-4530 is hsa-miR-4530, miR- 6798-5p is hsa-miR-6798-5p, miR- 6781-5p is hsa-miR-6781-5p, miR- 885 -3p is hsa-miR-885-3p, miR- 1273g-3p is hsa-miR-1273g-3p, miR-4787-3p is hsa-miR-4787-3p, is miR-4454 hsa is a -miR-4454, miR-4706 is hsa-miR-4706, miR- 1249-3p is hsa-miR-1249-3p, miR- 887-3p is located in hsa-miR-887-3p , miR-6786-5p is hsa-miR-6786-5p, miR- 1238 5p is hsa-miR-1238-5p, miR- 6749-5p is hsa-miR-6749-5p, miR- 6729-5p is hsa-miR-6729-5p, is miR-6825-5p is hsa-miR-6825-5p, miR- 663b is hsa-miR-663b, miR- 6858-5p is hsa-miR-6858-5p, miR- 4690-5p is hsa-miR-4690- is 5p, miR-6765-5p is hsa-miR-6765-5p, miR- 4710 is hsa-miR-4710, miR- 6775-5p is hsa-miR-6775-5p, miR- 371a-5p is hsa-miR-371a-5p, is miR-6816-5p is a sa-miR-6816-5p, miR- 296-3p is hsa-miR-296-3p, miR- 7977 is hsa-miR-7977, miR- 8069 is hsa-miR-8069, miR-6515-3p is hsa-miR-6515-3p, miR- 4687-5p is hsa-miR-4687-5p, miR- 1343-5p is hsa-miR-1343-5p, miR- 7110-5p is hsa-miR-7110-5p, miR- 4525 is hsa-miR-4525, miR- 3158-5p is hsa-miR-3158-5p, is miR-6787-5p hsa- It is a miR-6787-5p, miR-614 is hsa-miR-614, mi R-4689 is hsa-miR-4689, miR- 1185-2-3p is hsa-miR-1185-2-3p, miR- 1268b is hsa-miR-1268b, the miR-1228-3p a hsa-miR-1228-3p, miR- 1185-1-3p is hsa-miR-1185-1-3p, miR- 940 is hsa-miR-940, is miR-939-5p hsa- is a miR-939-5p, miR-6757-5p is hsa-miR-6757-5p, miR- 1275 is hsa-miR-1275, miR- 5001-5p is in hsa-miR-5001-5p Yes, miR-6826-5p is hsa-miR-6826-5p, is miR-6765-3p is a sa-miR-6765-3p, miR- 3679-3p is hsa-miR-3679-3p, miR- 4718 is hsa-miR-4718, miR- 4286 is hsa-miR-4286, miR-8059 is hsa-miR-8059, miR- 4447 is hsa-miR-4447, miR- 4448 is hsa-miR-4448, miR- 658 is hsa-miR-658, miR- 6766-3p is hsa-miR-6766-3p, miR- 197-5p is hsa-miR-197-5p, miR- 6887-5p is hsa-miR-6887-5p, miR- 6742- 5p is hsa-miR-6742-5p, miR- 6729-3p is h is a a-miR-6729-3p, miR- 5090 is hsa-miR-5090, miR- 7975 is hsa-miR-7975, miR- 4505 is hsa-miR-4505, miR- 6889- 5p is hsa-miR-6889-5p, miR- 4708-3p is hsa-miR-4708-3p, miR- 6131 is hsa-miR-6131, miR- 1225-3p is hsa-miR- is a 1225-3p, miR-6132 is hsa-miR-6132, miR- 4734 is hsa-miR-4734, miR- 3194-3p is hsa-miR-3194-3p, miR- 638 is is hsa-miR-638, miR- 2467-3p is hsa-miR Is a -2467-3p, miR-4728-5p is hsa-miR-4728-5p, miR- 5572 is hsa-miR-5572, miR- 6789-5p is located in hsa-miR-6789-5p , miR-8063 is hsa-miR-8063, miR- 4429 is hsa-miR-4429, miR- 6840-3p is hsa-miR-6840-3p, miR- 4476 is hsa-miR-4476 in and, miR-675-5p is hsa-miR-675-5p, miR- 711 is hsa-miR-711, miR- 6875-5p is hsa-miR-6875-5p, miR- 3160 -5p is hsa-miR-3160-5p, miR- 1908-5p is hs Is a -miR-1908-5p, miR-6726-5p is hsa-miR-6726-5p, miR- 1913 is hsa-miR-1913, miR- 8071 is hsa-miR-8071, miR -3648 is hsa-miR-3648, miR- 4732-5p is hsa-miR-4732-5p, miR- 4787-5p is hsa-miR-4787-5p, miR- 3917 is hsa-miR is -3917, miR-619-5p is hsa-miR-619-5p, miR- 1231 is hsa-miR-1231, miR- 342-5p is hsa-miR-342-5p, miR -4433a-5p is hsa-miR-4433a-5p, miR-676 -5p is hsa-miR-6766-5p, miR- 4707-5p is hsa-miR-4707-5p, miR- 7114-5p is hsa-miR-7114-5p, miR- 6872-3p There is a hsa-miR-6872-3p, miR- 6780b-5p is hsa-miR-6780b-5p, miR-7845-5p is hsa-miR-7845-5p, miR- 6798-3p is hsa -miR-6798-3p is, miR-665 is hsa-miR-665, miR- 6848-5p is hsa-miR-6848-5p, miR- 5008-5p is hsa-miR-5008-5p in it, miR-4294 is hsa-miR-4294, miR- 6511a-5p There is a hsa-miR-6511a-5p, miR-4435 is hsa-miR-4435, miR- 4747-3p is hsa-miR-4747-3p, miR- 6880-3p is hsa-miR-6880 is a -3p, miR-6869-5p is hsa-miR-6869-5p, miR- 7150 is hsa-miR-7150, miR- 1260a is hsa-miR-1260a, miR- 6877-5p There is a hsa-miR-6877-5p, miR- 6721-5p is hsa-miR-6721-5p, miR- 4656 is hsa-miR-4656, miR- 1229-5p is hsa-miR-1229 is a -5p, miR-4433a-3p is hsa-miR-443 is a a-3p, miR-4274 is hsa-miR-4274, miR- 4419b is hsa-miR-4419b, miR- 4674 is hsa-miR-4674, is miR-6893-5p hsa- is a miR-6893-5p, miR-6763-3p is hsa-miR-6763-3p, miR- 6762-5p is hsa-miR-6762-5p, miR- 6738-5p is hsa-miR- is a 6738-5p, miR-4513 is hsa-miR-4513, miR- 6746-5p is hsa-miR-6746-5p, miR- 6880-5p is hsa-miR-6880-5p, miR-4736 is hsa-miR-4736, miR- 718 is hsa is a miR-718, miR-6717-5p is hsa-miR-6717-5p, miR- 7847-3p is hsa-miR-7847-3p, miR- 760 is hsa-miR-760, miR-1199-5p is hsa-miR-1199-5p, miR- 6813-5p is hsa-miR-6813-5p, miR- 6769a-5p is hsa-miR-6769a-5p, miR- 1193 is hsa-miR-1193, miR- 7108-3p is hsa-miR-7108-3p, miR- 6741-5p is hsa-miR-6741-5p, miR- 4298 is hsa-miR- is 4298, miR-6796-3p is located in hsa-miR-6796-3p , MiR-4750-5p is hsa-miR-4750-5p, miR- 6785-5p is hsa-miR-6785-5p, miR- 1292-3p is hsa-miR-1292-3p, miR -4749-3p is hsa-miR-4749-3p
is, miR-6800-3p is hsa-miR-6800-3p, miR- 722-5p is hsa-miR-4722-5p, miR- 4746 -3p is hsa-miR-4746-3p, miR- 4450 is hsa-miR-4450, miR- 6795-5p is hsa-miR-6795-5p, miR- 365a-5p is hsa-miR is a -365a-5p, miR-498 is hsa-miR-498, miR- 67 7-5p is hsa-miR-6797-5p, miR- 1470 is hsa-miR-1470, miR- 6851-5p is hsa-miR-6851-5p, is miR-1247-3p hsa- is a miR-1247-3p, miR-5196-5p is hsa-miR-5196-5p, miR- 208a-5p is hsa-miR-208a-5p, miR-6842-5p is hsa-miR- is a 6842-5p, miR-150-3p is hsa-miR-150-3p, miR- 4534 is hsa-miR-4534, miR- 3135b is hsa-miR-3135b, is miR-3131 is hsa-miR-3131, miR- 4792 is in hsa-miR-4792 Ri, miR-6510-5p is hsa-miR-6510-5p, miR- 504-3p is hsa-miR-504-3p, miR- 3619-3p is hsa-miR-3619-3p, miR-671-5p is hsa-miR-671-5p, miR- 4667-5p is hsa-miR-4667-5p, miR- 4430 is hsa-miR-4430, miR- 3195 is hsa- is a miR-3195, miR-3679-5p is hsa-miR-3679-5p, miR- 6076 is hsa-miR-6076, miR- 6515-5p is hsa-miR-6515-5p, miR-6820-5p is hsa-miR-6820-5p, miR- 4634 is hsa Is a -miR-4634, miR-187-5p is hsa-miR-187-5p, miR- 6763-5p is hsa-miR-6763-5p, miR- 1908-3p is hsa-miR-1908 is a -3p, miR-1181 is hsa-miR-1181, miR- 6782-5p is hsa-miR-6782-5p, miR- 5010-5p is hsa-miR-5010-5p, miR -6870-5p is hsa-miR-6870-5p, miR- 6124 is hsa-miR-6124, miR- 1249-5p is hsa-miR-1249-5p, miR- 6511b-5p is hsa is a -miR-6511b-5p, miR- 1254 is in hsa-miR-1254 Ri, miR-4727-3p is hsa-miR-4727-3p, miR- 4259 is hsa-miR-4259, miR- 4771 is hsa-miR-4771, is miR-3622a-5p hsa- is a miR-3622a-5p, miR- 4480 is hsa-miR-4480, miR- 4740-5p is hsa-miR-4740-5p, miR- 6777-5p is in hsa-miR-6777-5p Yes, miR-6794-5p is hsa-miR-6794-5p, miR- 4687-3p is hsa-miR-4687-3p, miR- 6743-5p is hsa-miR-6743-5p, miR-6771-5p is hsa-miR-6771-5p, miR- 3 41 is hsa-miR-3141, miR- 3162-5p is hsa-miR-3162-5p, miR- 4271 is hsa-miR-4271, miR- 1227-5p is hsa-miR-1227- is 5p, miR-4257 is hsa-miR-4257, miR- 4270 is hsa-miR-4270, miR- 4516 is hsa-miR-4516, miR- 4651 is in hsa-miR-4651 Yes, miR-4725-3p is hsa-miR-4725-3p, miR- 6125 is hsa-miR-6125, miR- 6732-5p is hsa-miR-6732-5p, miR- 6791- 5p is hsa-miR-6791-5p, miR- 6819- 5p is hsa-miR-6819-5p, miR- 6891-5p is hsa-miR-6891-5p, miR- 7108-5p is hsa-miR-7108-5p, is miR-7109-5p a hsa-miR-7109-5p, miR- 642b-3p is hsa-miR-642b-3p, miR-642a-3p is hsa-miR-642a-3p, according to (8) devices.
[0039]
(10) The nucleic acid polynucleotide in any of the following (a) -
(e): (a) in the nucleotide sequence or the nucleotide sequence shown in any of SEQ ID NO: 1 to 247,251 and 268 polynucleotides, a variant thereof u is the nucleotide sequence is t, a derivative thereof, or a fragment thereof comprising 15 or more continuous
nucleotides, represented by any one of (b) SEQ ID NO: 1 to 247,251 and 268 polynucleotide comprising a nucleotide sequence,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (c) SEQ ID NO: 1 to 247,251 and 268 , a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous
nucleotides, represented by any of (d) SEQ ID NO: 1 to 247,251 and 268 Polynucleotide u in the nucleotide sequence or the nucleotide sequence comprises a nucleotide sequence complementary to the nucleotide sequence is t, and
(e) above (a) in any of the polynucleotides under stringent conditions of ~ (d) hybridizing polynucleotide,
a polynucleotide selected from the group consisting of, according to (8) or (9) devices.
[0040]
(11) the device is another ovarian tumor marker, miR-320a, miR-663a, miR-328-5p, miR-128-2-5p, miR-125a-3p, miR-191-5p, miR -92b-5p, miR-296-5p, miR-1246, miR-92a-2-5p, miR-128-1-5p, miR-1290, miR-211-3p, miR-744-5p, miR-135a -3p, miR-451a, miR-625-3p, miR-92a-3p, miR-422a, miR-483-5p, miR-652-5p, miR-24-3p, miR-23b-3p, miR-23a -3p, miR-92b-3p, at least one polynucleotide selected from miR-22-3p, or 該Po Further comprising a complementary strand capable of specifically binding a nucleic acid of the nucleotide A device according to any one of (8) to (10).
[0041]
(12) miR-320a is hsa-miR-320a, miR-663a is hsa-miR-663a, miR-328-5p is hsa-miR-328-5p, miR-128-2-5p There is a hsa-miR-128-2-5p, miR-125a-3p is hsa-miR-125a-3p, miR-191-5p is hsa-miR-191-5p, miR-92b-5p There is a hsa-miR-92b-5p, miR-296-5p is hsa-miR-296-5p, miR-1246 is hsa-miR-1246, miR-92a-2-5p is hsa-miR is a -92a-2-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-1290 Is hsa-miR-1290, miR-211-3p is hsa-miR-211-3p, miR-744-5p is hsa-miR-744-5p, miR-135a-3p is hsa-miR- a 135a-3p, miR-451a is hsa-miR-451a, miR-625-3p is hsa-miR-625-3p, miR-92a-3p is hsa-miR-92a-3p, miR-422a is hsa-miR-422a, miR-483-5p is hsa-miR-483-5p, miR-652-5p is hsa-miR-652-5p, is miR-24-3p is hsa-miR-24-3p, miR-23b-3p is hsa-miR-23b-3p, miR-2 a-3p is hsa-miR-23a-3p, miR-92b-3p is hsa-miR-92b-3p, miR-22-3p is hsa-miR-22-3p, (11) the device according.
[0042]
(13) The nucleic acid polynucleotide in any of the following (f) -
(j): (f) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 nucleotide sequence or represented by any one of the ~ 275 the nucleotide u in sequence consisting of the nucleotide sequence is t polynucleotides, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous
nucleotides, (g) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ a polynucleotide comprising a nucleotide sequence represented by any one of
275, u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (h) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 a polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence, the fragment comprising the variant, derivative, or 15 or more contiguous bases
(I) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence shown in any of 275, and
( j) above (f) any of the polynucleotides under stringent conditions with a polynucleotide hybridizing of ~ (i),
a polynucleotide selected from the consisting of group, according to (11) or (12) device.
[0043]
(14) The device is a device for the measurement by hybridization techniques, according to any one of (8) to (13) device.
[0044]
(15) The hybridization techniques, a nucleic acid array technology, as described in (14) device.
[0045]
(16) The device (8) or (9) at least two polynucleotides selected from all ovarian tumor markers described, or respectively capable of specifically binding at least two complementary strands of the polynucleotide one of containing nucleic acid according to any one of (8) to (15) device.
[0046]
(17) The sample of the subject, ovarian tumor marker, miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940 -5p, miR-1307-3p, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p , miR-1343-3p, miR-4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, miR-1260b, miR-4258, miR -4697-5p, miR-1469, miR-4 15, miR-6861-5p, miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781- 5p, miR-885-3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238- 5p, miR-6749-5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775- 5p, miR-371a-5p, miR-6816-5p, m R-296-3p, miR-7977, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR- 6787-5p, miR-614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR- 6757-5p, miR-1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR- 4448, miR-658, miR-6766-3p, miR-1 97-5p, miR-6887-5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR-6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR-6840-3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR- 1913, miR-8071, miR-3648, miR 4732-5p, miR-4787-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR- 7114-5p, miR-6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR- 6511a-5p, miR-4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p, miR-4433a-3 , MiR-4274, miR-4419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880 -5p, miR-4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR -7108-3p, miR-6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p , miR-4722-5p, miR-4746-3p , MiR-4450, miR-6795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR -208a-5p, miR-6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p , miR-671-5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187 -5p, miR-6763-5p, miR-1908- p, miR-1181, miR-6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR-4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR- 6771-5p, miR-3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR-679 -5p, miR-6819-5p, miR-6891-5p, miR-7108-5p, miR-7109-5p, the expression level of at least one polynucleotide that miR-642b-3p, selected from miR-642a-3p the measures, that the subject using the expression amount is the measurement is afflicted with ovarian cancer, or comprises assessing the in vitro that does not suffer from ovarian tumors, the detection method of ovarian tumors.
[0047]
(18) 卵 巣 腫 瘍 マ ー カ ー で あ る, miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307 -3P, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p , miR-4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, 1260b-miR, miR-4258, miR-4697-5p, miR -1469, miR-4515, miR-686 -5p, miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885 -3P, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749 -5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a -5p, miR-6816-5p, miR-296-3p, m R-7977, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR 614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR 1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR-6766-3p, miR-197-5p, miR-6 887-5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR-6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR 6840-3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR-3648, miR-4732-5p, mi -4787-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR -6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR -4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p , miR-4433a-3p, miR-4274, iR-4419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR 4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR-6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722- 5p, miR-4746-3p, miR-4450, m iR 6795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR-6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671- 5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR 6763-5p, miR-1908-3p, miR-1181 miR-6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR 4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR 3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR-6791-5p, miR-68 9-5p, miR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p 及 び miR-642a-3p か ら 選 択 さ れ る 少 な く と も 1 つ 又 は 少 な く と も 2 つ の ポ リ ヌ ク レ オ チ ド, 又 は 当 該 ポ リヌ ク レ オ チ ド の 相 補 鎖 の そ れ ぞ れ と 特異 的 に 結合 可能 な 核酸 を 含 む, (1) ~ (7) の い ず れ か に 記載 の キ ッ ト 又 は (8) ~ (16) の い ず れ か に 記載 の デ バ イ ス を 用 い て,被 験 体 の 検 体 に お け る 標的 核酸 の 発 現 量 を 測定 し, 該 測定 さ れ た 発 現 量 と, 同 様 に 測定 さ れ た 健 常 者 の 対 照 発 現 量 と を 用 い て 被 験 体 が 卵 巣 腫 瘍 に 罹患 し て い る こ と, 又 は卵 巣 腫 瘍 に 罹患 し て い な い こ と を in vitro で 評 価 す る こ と を 含 む, 卵 巣 腫 瘍 の 検 出 方法.
[0048]
(19) 卵 巣 腫 瘍 マ ー カ ー で あ る, miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307 -3P, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p , miR-4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, 1260b-miR, miR-4258, miR-4697-5p, miR -1469, miR-4515, miR-686 -5p, miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885 -3P, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749 -5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a -5p, miR-6816-5p, miR-296-3p, m R-7977, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR 614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR 1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR-6766-3p, miR-197-5p, miR-6 887-5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR-6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR 6840-3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR-3648, miR-4732-5p, mi -4787-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR -6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR -4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p , miR-4433a-3p, miR-4274, iR-4419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR 4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR-6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722- 5p, miR-4746-3p, miR-4450, m iR 6795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR-6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671- 5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR 6763-5p, miR-1908-3p, miR-1181 miR-6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR 4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR 3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR-6791-5p, miR-68 9-5p, miR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p, miR-642a-3p か ら 選 択 さ れ る 少 な く と も 1 つ 又 は 少 な く と も 2 つ の ポ リ ヌ ク レ オ チ ド, 又 は 当 該 ポ リヌ ク レ オ チ ド の 相 補 鎖 の そ れ ぞ れ と 特異 的 に 結合 可能 な 核酸 を 含 む, (1) ~ (7) の い ず れ か に 記載 の キ ッ ト 又 は (8) ~ (16) の い ず れ か に 記載 の デ バ イ ス を 用 い て 被 験体 の 検 体 に お け る 標的 遺 伝 子 の 発 現 量 を 測定 し, 卵 巣 腫 瘍 を 有 す る こ と が 既知 で あ る 被 験 体 由来 の 検 体 の 遺 伝 子 発 現 量 と 卵 巣 腫 瘍 に 罹患 し て い な い 被 験 体 由来 の 検 体 の 遺 伝 子 発 現 量 を 教師サ ン プ ル と し て 作成 さ れ た, か つ 卵 巣 腫 瘍 の 存在 ま た は 不 存在 を 区別 的 に 判別 す る こ と が 可能 で あ る 判別 式 に, 上 記 被 験 体 由来 の 検 体 に お け る 標的 遺 伝 子 の 発 現 量 を 代 入 し, そ れ に よ っ て, 卵 巣 腫 瘍 の 存在 又 は 不 存在 を in vitro で 評 価 す る こ と を 含 む, 卵 巣 腫 瘍 の 検 出 方法.
[0049]
(20) miR-4675 is hsa-miR-4675, miR- 4783-3p is hsa-miR-4783-3p, miR- 1228-5p is hsa-miR-1228-5p, miR- 4532 There is a hsa-miR-4532, miR- 6802-5p is hsa-miR-6802-5p, miR- 6784-5p is hsa-miR-6784-5p, miR- 3940-5p is hsa-miR is a -3940-5p, miR-1307-3p is hsa-miR-1307-3p, miR- 8073 is hsa-miR-8073, miR- 3184-5p is located in hsa-miR-3184-5p , miR-1233-5p is hsa-miR-1233-5p, miR- 60 8 is hsa-miR-6088, miR- 5195-3p is hsa-miR-5195-3p, miR- 320b is hsa-miR-320b, miR- 4649-5p is hsa-miR-4649- is 5p, miR-6800-5p is hsa-miR-6800-5p, miR- 1343-3p is hsa-miR-1343-3p, miR- 4730 is hsa-miR-4730, miR- 6885-5p is hsa-miR-6885-5p, miR- 5100 is hsa-miR-5100, miR- 1203 is hsa-miR-1203, miR- 6756-5p is hsa-miR-6756- is 5p, miR-373-5p is located in hsa-miR-373-5p miR-1268a is hsa-miR-1268a, miR- 1260b is hsa-miR-1260b, miR- 4258 is hsa-miR-4258, miR- 4697-5p is in hsa-miR-4697-5p Yes, miR-1469 is hsa-miR-1469, miR- 4515 is hsa-miR-4515, miR- 6861-5p is hsa-miR-6861-5p, is miR-6821-5p hsa- is a miR-6821-5p, miR-575 is hsa-miR-575, miR- 6805-5p is hsa-miR-6805-5p, miR- 4758-5p is in hsa-miR-4758-5p Yes, miR-3663-3p is hsa-miR-3663-3 a p, miR-4530 is hsa-miR-4530, miR- 6798-5p is hsa-miR-6798-5p, miR- 6781-5p is hsa-miR-6781-5p, miR- 885-3p is hsa-miR-885-3p, miR- 1273g-3p is hsa-miR-1273g-3p, miR-4787-3p is hsa-miR-4787-3p, is miR-4454 is hsa-miR-4454, miR- 4706 is hsa-miR-4706, miR- 1249-3p is hsa-miR-1249-3p, miR- 887-3p is in hsa-miR-887-3p There, miR-6786-5p is hsa-miR-6786-5p, miR- 123 -5p is hsa-miR-1238-5p, miR- 6749-5p is hsa-miR-6749-5p, miR- 6729-5p is hsa-miR-6729-5p, miR- 6825-5p There is a hsa-miR-6825-5p, miR- 663b is hsa-miR-663b, miR- 6858-5p is hsa-miR-6858-5p, miR- 4690-5p is hsa-miR-4690 is a -5p, miR-6765-5p is hsa-miR-6765-5p, miR- 4710 is hsa-miR-4710, miR- 6775-5p is hsa-miR-6775-5p, miR -371a-5p is hsa-miR-371a-5p, miR-6816-5p is hsa-miR-6816-5p, miR- 296-3p is hsa-miR-296-3p, miR- 7977 is hsa-miR-7977, miR- 8069 is hsa-miR-8069, miR-6515-3p is hsa-miR-6515-3p, miR- 4687-5p is hsa-miR-4687-5p, miR- 1343-5p is hsa-miR-1343-5p, miR- 7110-5p is hsa-miR-7110-5p, miR- 4525 is hsa-miR-4525, miR- 3158-5p is hsa-miR-3158-5p, is miR-6787-5p hsa- a miR-6787-5p, miR-614 is hsa-miR-614, m iR-4689 is hsa-miR-4689, miR- 1185-2-3p is hsa-miR-1185-2-3p, miR- 1268b is hsa-miR-1268b, is miR-1228-3p a hsa-miR-1228-3p, miR- 1185-1-3p is hsa-miR-1185-1-3p, miR- 940 is hsa-miR-940, is miR-939-5p hsa- is a miR-939-5p, miR-6757-5p is hsa-miR-6757-5p, miR- 1275 is hsa-miR-1275, miR- 5001-5p is in hsa-miR-5001-5p Yes, miR-6826-5p is hsa-miR-6826-5p, miR- 6765-3p is hsa-miR-6765-3p, miR- 3679-3p is hsa-miR-3679-3p, miR- 4718 is hsa-miR-4718, miR- 4286 is hsa-miR-4286, miR-8059 is hsa-miR-8059, miR- 4447 is hsa-miR-4447, miR- 4448 is hsa-miR-4448, miR- 658 is hsa-miR-658, miR- 6766-3p is hsa-miR-6766-3p, miR- 197-5p is hsa-miR-197-5p, miR- 6887-5p is hsa-miR-6887-5p, miR- 6742- 5p is hsa-miR-6742-5p, is miR-6729-3p is a sa-miR-6729-3p, miR- 5090 is hsa-miR-5090, miR- 7975 is hsa-miR-7975, miR- 4505 is hsa-miR-4505, miR- 6889- 5p is hsa-miR-6889-5p, miR- 4708-3p is hsa-miR-4708-3p, miR- 6131 is hsa-miR-6131, miR- 1225-3p is hsa-miR- is a 1225-3p, miR-6132 is hsa-miR-6132, miR- 4734 is hsa-miR-4734, miR- 3194-3p is hsa-miR-3194-3p, miR- 638 is is hsa-miR-638, miR- 2467-3p is hsa-mi An R-2467-3p, miR-4728-5p is hsa-miR-4728-5p, miR- 5572 is hsa-miR-5572, miR- 6789-5p is in hsa-miR-6789-5p Yes, miR-8063 is hsa-miR-8063, miR- 4429 is hsa-miR-4429, miR- 6840-3p is hsa-miR-6840-3p, miR- 4476 is hsa-miR- is 4476, miR-675-5p is hsa-miR-675-5p, miR- 711 is hsa-miR-711, miR- 6875-5p is hsa-miR-6875-5p, miR- 3160-5p is hsa-miR-3160-5p, miR- 1908-5p is h is a a-miR-1908-5p, miR- 6726-5p is hsa-miR-6726-5p, miR- 1913 is hsa-miR-1913, miR- 8071 is hsa-miR-8071, miR-3648 is hsa-miR-3648, miR- 4732-5p is hsa-miR-4732-5p, miR- 4787-5p is hsa-miR-4787-5p, miR- 3917 is hsa- is a miR-3917, miR-619-5p is hsa-miR-619-5p, miR- 1231 is hsa-miR-1231, miR- 342-5p is hsa-miR-342-5p, miR-4433a-5p is hsa-miR-4433a-5p, miR-67 6-5p is hsa-miR-6766-5p, miR- 4707-5p is hsa-miR-4707-5p, miR- 7114-5p is hsa-miR-7114-5p, miR- 6872- 3p is hsa-miR-6872-3p, miR- 6780b-5p is hsa-miR-6780b-5p, miR-7845-5p is hsa-miR-7845-5p, is miR-6798-3p is hsa-miR-6798-3p, miR- 665 is hsa-miR-665, miR- 6848-5p is hsa-miR-6848-5p, miR- 5008-5p is hsa-miR-5008- is 5p, miR-4294 is hsa-miR-4294, miR- 6511a-5 p is hsa-miR-6511a-5p, miR-4435 is hsa-miR-4435, miR- 4747-3p is hsa-miR-4747-3p, miR- 6880-3p is hsa-miR- is a 6880-3p, miR-6869-5p is hsa-miR-6869-5p, miR- 7150 is hsa-miR-7150, miR- 1260a is hsa-miR-1260a, miR- 6877- 5p is hsa-miR-6877-5p, miR- 6721-5p is hsa-miR-6721-5p, miR- 4656 is hsa-miR-4656, miR- 1229-5p is hsa-miR- is a 1229-5p, miR-4433a-3p is hsa-miR-44 A 3a-3p, miR-4274 is hsa-miR-4274, miR- 4419b is hsa-miR-4419b, miR- 4674 is hsa-miR-4674, the miR-6893-5p hsa- is a miR-6893-5p, miR-6763-3p is hsa-miR-6763-3p, miR- 6762-5p is hsa-miR-6762-5p, miR- 6738-5p is hsa-miR- is a 6738-5p, miR-4513 is hsa-miR-4513, miR- 6746-5p is hsa-miR-6746-5p, miR- 6880-5p is hsa-miR-6880-5p, miR-4736 is hsa-miR-4736, miR- 718 is hs Is a -miR-718, miR-6717-5p is hsa-miR-6717-5p, miR- 7847-3p is hsa-miR-7847-3p, miR- 760 is located in the hsa-miR-760 , miR-1199-5p is hsa-miR-1199-5p, miR- 6813-5p is hsa-miR-6813-5p, miR- 6769a-5p is hsa-miR-6769a-5p, miR -1193 is hsa-miR-1193, miR- 7108-3p is hsa-miR-7108-3p, miR- 6741-5p is hsa-miR-6741-5p, miR- 4298 is hsa-miR is -4298, miR-6796-3p is hsa-miR-6796-3p der Ri, miR-4750-5p is hsa-miR-4750-5p, miR- 6785-5p is hsa-miR-6785-5p, miR- 1292-3p is hsa-miR-1292-3p, miR-4749-3p is hsa-miR-4749-3
is a p, miR-6800-3p is hsa-miR-6800-3p, miR- 722-5p is hsa-miR-4722-5p, miR -4746-3p is hsa-miR-4746-3p, miR- 4450 is hsa-miR-4450, miR- 6795-5p is hsa-miR-6795-5p, miR- 365a-5p is hsa It is a -miR-365a-5p, miR- 498 is hsa-miR-498, miR- 6 797-5p is hsa-miR-6797-5p, miR- 1470 is hsa-miR-1470, miR- 6851-5p is hsa-miR-6851-5p, is miR-1247-3p hsa- is a miR-1247-3p, miR-5196-5p is hsa-miR-5196-5p, miR- 208a-5p is hsa-miR-208a-5p, miR-6842-5p is hsa-miR- is a 6842-5p, miR-150-3p is hsa-miR-150-3p, miR- 4534 is hsa-miR-4534, miR- 3135b is hsa-miR-3135b, is miR-3131 is hsa-miR-3131, miR- 4792 is hsa-miR-4792 Yes, miR-6510-5p is hsa-miR-6510-5p, miR- 504-3p is hsa-miR-504-3p, miR- 3619-3p is hsa-miR-3619-3p, miR-671-5p is hsa-miR-671-5p, miR- 4667-5p is hsa-miR-4667-5p, miR- 4430 is hsa-miR-4430, miR- 3195 is hsa- is a miR-3195, miR-3679-5p is hsa-miR-3679-5p, miR- 6076 is hsa-miR-6076, miR- 6515-5p is hsa-miR-6515-5p, miR-6820-5p is hsa-miR-6820-5p, miR- 4634 is h is a a-miR-4634, miR- 187-5p is hsa-miR-187-5p, miR- 6763-5p is hsa-miR-6763-5p, miR- 1908-3p is hsa-miR- is a 1908-3p, miR-1181 is hsa-miR-1181, miR- 6782-5p is hsa-miR-6782-5p, miR- 5010-5p is hsa-miR-5010-5p, miR-6870-5p is hsa-miR-6870-5p, miR- 6124 is hsa-miR-6124, miR- 1249-5p is hsa-miR-1249-5p, is miR-6511b-5p is hsa-miR-6511b-5p, miR-1254 is hsa-miR-1254 In it, miR-4727-3p is hsa-miR-4727-3p, miR- 4259 is hsa-miR-4259, miR- 4771 is hsa-miR-4771, miR- 3622a-5p is hsa is a -miR-3622a-5p, miR- 4480 is hsa-miR-4480, miR- 4740-5p is hsa-miR-4740-5p, miR- 6777-5p is hsa-miR-6777-5p in it, miR-6794-5p is hsa-miR-6794-5p, miR- 4687-3p is hsa-miR-4687-3p, miR- 6743-5p is located in hsa-miR-6743-5p , miR-6771-5p is hsa-miR-6771-5p, miR- 141 is hsa-miR-3141, miR- 3162-5p is hsa-miR-3162-5p, miR- 4271 is hsa-miR-4271, miR- 1227-5p is hsa-miR-1227- is 5p, miR-4257 is hsa-miR-4257, miR- 4270 is hsa-miR-4270, miR- 4516 is hsa-miR-4516, miR- 4651 is in hsa-miR-4651 Yes, miR-4725-3p is hsa-miR-4725-3p, miR- 6125 is hsa-miR-6125, miR- 6732-5p is hsa-miR-6732-5p, miR- 6791- 5p is hsa-miR-6791-5p, miR- 681 -5p is hsa-miR-6819-5p, miR- 6891-5p is hsa-miR-6891-5p, miR- 7108-5p is hsa-miR-7108-5p, miR- 7109-5p There is a hsa-miR-7109-5p, miR- 642b-3p is hsa-miR-642b-3p, miR-642a-3p is hsa-miR-642a-3p, (17) ~ (19) the method according to any one of.
[0050]
(21) The nucleic acid polynucleotide in any of the following (a) -
(e): (a) nucleotide sequence shown in any of SEQ ID NO: 1 to 247,251 and 268, or the nucleotide sequence u nucleotide sequence is t, a polynucleotide consisting of a variant, derivative, or fragment thereof comprising 15 or more continuous
nucleotides, tables in any one of (b) SEQ ID NO: 1 to 247,251 and 268 polynucleotides comprising a nucleotide sequence that is
a nucleotide sequence, a complementary nucleotide sequence and u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (c) SEQ ID NO: 1 to 247,251 and 268 polynucleotide consisting, variants, fragments thereof containing the derivative, or 15 or more continuous
nucleotides, either (d) SEQ ID NO: 1 to 247,251 and 268 Polynucleotide u in the nucleotide sequence or the nucleotide sequence represented comprises a nucleotide sequence, a complementary nucleotide sequence is a t on whether, and
(e) any of the polynucleotides described above (a) ~ (d) a polynucleotide hybridizing under stringent conditions,
a polynucleotide selected from the group consisting of a method according to any one of (17) to (19).
[0051]
(22) The kit or device is another ovarian tumor marker, miR-320a, miR-663a, miR-328-5p, miR-128-2-5p, miR-125a-3p, miR-191-5p , miR-92b-5p, miR-296-5p, miR-1246, miR-92a-2-5p, miR-128-1-5p, miR-1290, miR-211-3p, miR-744-5p, miR -135a-3p, miR-451a, miR-625-3p, miR-92a-3p, miR-422a, miR-483-5p, miR-652-5p, miR-24-3p, miR-23b-3p, miR -23a-3p, miR-92b-3p, at least one polynucleotide selected from miR-22-3p Or further comprising a complementary strand capable of specifically binding a nucleic acid of the polynucleotide, the method according to any one of (17) to (21).
[0052]
(23) miR-320a is hsa-miR-320a, miR-663a is hsa-miR-663a, miR-328-5p is hsa-miR-328-5p, miR-128-2-5p There is a hsa-miR-128-2-5p, miR-125a-3p is hsa-miR-125a-3p, miR-191-5p is hsa-miR-191-5p, miR-92b-5p There is a hsa-miR-92b-5p, miR-296-5p is hsa-miR-296-5p, miR-1246 is hsa-miR-1246, miR-92a-2-5p is hsa-miR is a -92a-2-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-1290 Is hsa-miR-1290, miR-211-3p is hsa-miR-211-3p, miR-744-5p is hsa-miR-744-5p, miR-135a-3p is hsa-miR- a 135a-3p, miR-451a is hsa-miR-451a, miR-625-3p is hsa-miR-625-3p, miR-92a-3p is hsa-miR-92a-3p, miR-422a is hsa-miR-422a, miR-483-5p is hsa-miR-483-5p, miR-652-5p is hsa-miR-652-5p, is miR-24-3p is hsa-miR-24-3p, miR-23b-3p is hsa-miR-23b-3p, miR-2 a-3p is hsa-miR-23a-3p, miR-92b-3p is hsa-miR-92b-3p, miR-22-3p is hsa-miR-22-3p, (22) the method described.
[0053]
(24) The nucleic acid polynucleotide in any of the following (f) -
(j): (f) the nucleotide sequence shown in any of SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275, or a nucleotide sequence u in the nucleotide sequence is t, a polynucleotide consisting of a variant, derivative, or fragment thereof comprising 15 or more continuous
nucleotides, (g) SEQ ID NO: 248 ~ 250, 252 ~ 267 and a polynucleotide comprising the nucleotide sequence shown in any
269-275 is u in the nucleotide sequence or the nucleotide sequence represented by any one of (h) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 nucleotide sequence is t, the polynucleotide comprising a nucleotide sequence complementary, a variant thereof, derivatives thereof, or 15 or more contiguous bases Fragment,
containing the nucleotide sequence, a complementary nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (i) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 polynucleotides, and
(j) above (f) ~ any polynucleotide and a polynucleotide hybridizing under stringent conditions (i),
a polynucleotide selected from the group consisting of, (22) or ( the method according to 23).
[0054]
(25) the subject is a human, the method according to any one of (17) to (24).
[0055]
(26) The specimen is blood, serum or plasma, the method according to any one of (17) to (25).
[0056]
Terms used herein have the following definitions.
, Polynucleotides, DNA, by abbreviations, such as RNA shall follow conventional in the "Guidelines for Preparation of the specification or the like comprising a base sequence or amino acid sequence" (Japan Patent Office ed.) And art .
[0057]
A "polynucleotide" as used herein, RNA, DNA, and none of the RNA / DNA (chimeric) used for encompasses nucleic acids. Note that the above-mentioned DNA, include cDNA, genomic DNA, and even synthetic DNA is. Also in the above RNA, total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, which include any non-coding RNA and synthetic RNA. "Synthetic DNA" and "synthetic RNA" herein, on the basis of a predetermined nucleotide sequence (either native sequence or a non-natural sequence good.), For example using an automatic nucleic acid synthesizer, artificial It refers to a fabricated DNA and RNA. "Non-naturally occurring sequence" herein is intended to be used in the broad sense, differs from the native sequence, e.g., one or more nucleotide substitutions, deletions, insertions and / or sequence comprising additional ( that encompasses variant sequence), sequences comprising one or more modified nucleotides (i.e., modified sequence), and the like. Further, in this specification, the polynucleotide is used nucleic interchangeably.
[0058]
The term "fragment" as used herein, is a polynucleotide having a nucleotide sequence of contiguous portion of a polynucleotide, 15 bases or more, it is desirable that preferably 17 bases or more, more preferably having 19 or more bases in length .
[0059]
"Gene" as used herein, RNA, and not double-stranded DNA only, include the single-stranded DNA, such as plus strand constituting it (or sense strand) or complementary strand (or antisense strand) used is intended to. Also not to be particularly limited by its length. Thus, a "gene", as used herein, unless otherwise noted, single-stranded DNA (complementary with double-stranded DNA, single-stranded DNA (plus strand) complementary to sequences with the positive strand containing a human genomic DNA chain), including cDNA, micro RNA (miRNA), and fragments thereof, the human genome, and none of these transcripts. Also the "gene" is not only a "gene" represented by a specific nucleotide sequence (or SEQ ID NO:), RNA RNA and biological functions encoded by these are equivalent, for example, homologs (i.e., homologs or orthologs), variants such as genetic polymorphisms, and "nucleic acid" encoding derivatives are included. Such homologues, the "nucleic acid" encoding a variant or derivative, specifically, under stringent conditions as described later, a nucleotide sequence, or the base represented by any of SEQ ID NO: 1-842 u has a nucleotide sequence, the complementary sequence hybridizing to the nucleotide sequence of t in the sequence may include "nucleic acid". Incidentally, a "gene" does not matter whether another functional area, may comprise for example expression control region, coding region, exon or intron. Also, "gene" may be included in the cell, are released to the outside of the cell may be present alone, or may be in a state of being encapsulated in vesicles called exosomes.
[0060]
The "exosomes" or "exosomes" in the present specification, a vesicle, wrapped in a lipid bilayer that is secreted from the cell. Exosomes derived from multivesicular endosomes, sometimes when they are released into the extracellular environment, including RNA, biological materials, such as "gene" and protein such as DNA therein. Exosomes blood, serum, plasma, serum, it is known to be contained in the body fluid such as lymph.
[0061]
The "transcript" as used herein, refers to a DNA sequence of a gene of RNA synthesized as a template. Binds to a site where RNA polymerase is referred to as a promoter upstream of the gene, RNA is synthesized in a manner going way 3 'end is bound ribonucleotides be complementary to the base sequence of DNA. The RNA not only gene itself, the expression control region, the coding region includes the entire sequence from the transcription initiation point, including exons or introns up to end of the poly A sequence.
[0062]
Further, "micro RNA (miRNA)", as used herein, unless otherwise noted, are transcribed as RNA precursor hairpin-like structure, is cut by dsRNA cleavage enzyme having RNase III cleavage activity, a protein complex called RISC incorporated into and used with the intention of non-coding RNA between 15 and 25 bases involved in mRNA translation inhibition. The "miRNA" as used herein not only "miRNA" represented by a specific nucleotide sequence (or SEQ ID NO:) contains a precursor of the "miRNA" (pre-miRNA, pri-miRNA) encompasses these miRNA and biological functions encoded by the miRNA is equivalent, for example, homologs (i.e., homologs or orthologs), genetic variants such as polymorphisms, and "miRNA" also encoding derivatives. Such precursors, congeners, as "miRNA" encoding variants or derivatives, specifically, can be identified by miRBase release 21 (http://www.mirbase.org/), described later under stringent conditions, it may be mentioned "miRNA" having any complementary sequences that hybridize to the nucleotide sequence of the specific nucleotide sequence shown in any of SEQ ID NO: 1-842. Furthermore, "miRNA" as used herein may be a gene product of miR genes, such gene products are mature miRNA (e.g., involved in translational repression of the mRNA as described above 15 ~ 25 includes a base, or 19 to 25 bases, non-coding RNA) or miRNA precursor (e.g., the pre-miRNA or pri-miRNA like).
[0063]
"Probe" as used herein encompasses polynucleotides and / or complementary to the polynucleotide used for specifically detecting the resulting RNA or polynucleotides derived therefrom by the expression of the gene.
[0064]
The term "primer" as used herein encompasses, for specifically recognizing the resulting RNA or polynucleotides derived therefrom by expression of a gene, to amplify, the contiguous polynucleotide and / or a polynucleotide complementary.
[0065]
Here complementary polynucleotide (complementary strand, reverse strand) to the base sequence u is t in the nucleotide sequence or the nucleotide sequence as defined by any of SEQ ID NO: 1 to 842 from the consisting of polynucleotides full-length sequence, or subsequence thereof, (for convenience here, this is referred to as positive strand) a relative: T (U), G: based on the base pair relation such C, in the base complementary relationship It refers to a polynucleotide. However, such a complementary strand is not limited to the case of forming a base sequence completely complementary to the sequence of the positive strand of interest, those having a complementary relationship to the extent that can hybridize with the positive strand under stringent conditions to target it may be.
[0066]
The "stringent conditions" as used herein, than the nucleic acid probe to other sequences, detectable by a large degree (e.g. average background measurements + background SEM × 2 or more measurement values of ) in refers to hybridizing conditions to its target sequence. Stringent conditions are sequence-dependent and will be different depending on the environment hybridization is performed. By controlling the stringency of the hybridization and / or wash conditions, target sequences can be identified which are 100% complementary to the nucleic acid probe. Specific examples of the "stringent conditions" will be described later.
The "Tm value" herein, the double-stranded portion of the polynucleotide is denatured into single-stranded, double-stranded and single-stranded 1: means the temperature that exists in a ratio.
[0067]
A "variant" as used herein, in the case of nucleic acids, polymorphisms, variants of native caused such a mutation, or nucleotide sequence represented by SEQ ID NO: or u in the nucleotide sequence is t nucleotide sequence, or base deletion of 1, 2 or 3 or more at its partial sequence (e.g., one to several), substitution, addition or variants including insertion, or any of the sequences of SEQ ID NO: 1-275 nucleotide sequence or nucleotide sequence u in the nucleotide sequence is t, or one or more base deletion in its partial sequence, substitution, addition or variant comprising an insertion of the precursor RNA (premature miRNA), Alternatively the respective nucleotide sequence or subsequence thereof and about 90%, about 95% or more, about 97% or more, about 98% or more, mutants showing about 99% or more% identity, or It refers to hybridizing nucleic acids under stringent conditions of the nucleotide sequence or a polynucleotide or oligonucleotide as previously defined comprising a subsequence thereof.
[0068]
The term "several" as used herein, means about 10,9,8,7,6,5,4,3 or two integers.
[0069]
As used herein, mutants, site-directed mutagenesis may be made using well known techniques, such as mutagenesis method using PCR method.
[0070]
"% Identity" herein is by BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi) and FASTA (http://www.genome.jp/tools/fasta/) . protein or using search system gene, and introducing gaps, or not introducing gaps, can be determined (Zheng Zhang et al., 2000, J.Comput.Biol, 7 vol, P203-214; . Altschul, S.F et al., 1990, Journal of Molecular Biology, 215 Volume, p403-410;. Pearson, W.R et al., 1988, Proc.Natl.Acad.Sci.U.S.A,. Chapter 85 Volume, p2444-2448 ).
[0071]
"Derivative" as used herein, modified nucleic acids, but not limited to for example, labeled derivatives due fluorophore, modified nucleotides (e.g. halogen, alkyl such as methyl, alkoxy such as methoxy, thio, groups such as carboxymethyl reconstruction of nucleotides and bases including double bond saturation, deamination, derivatives containing nucleotides, etc.) that received such substitution of sulfur molecules oxygen molecules, PNA (peptide nucleic acid; Nielsen, P.E. et al., 1991, Science, 254 vol, p1497-500), LNA (locked nucleic acid;. Obika, S, et al., refers to 1998, Tetrahedron Lett, 39 vol, P5401-5404), and the like..
[0072]
The polynucleotide is selected from the miRNA ovarian tumor marker described hereinabove, or the polynucleotide complementary strand capable of binding specifically to the "nucleic acid", or capable of detecting the polynucleotide "nucleic acid" is a nucleic acid that has been synthesized or prepared, for example, include a "nucleic acid probe" or "primer", in order to detect the presence or absence of ovarian tumors in a subject, or the presence or absence of diseased ovarian tumor, the degree of morbidity, the degree of presence and improved improvement of ovarian tumors, in order to diagnose susceptibility to treatment of ovarian tumors, or preventing ovarian tumors, to screen for useful candidates for improving or treating, directly or indirectly use that. These in vivo in relation to the onset of ovarian tumors, especially blood, the transcript or its cDNA synthetic nucleic acid represented by any of SEQ ID NO: 1 to 842 in the sample of body fluid such as specifically recognizes such as urine nucleotides capable of binding to, including oligonucleotides and polynucleotides. These nucleotides, oligonucleotides and polynucleotides, in a living body based on the properties, as a probe for detecting the gene expressed in such tissues or the cells and also for amplifying the gene expressed in vivo it can be effectively used as a primer.
[0073]
The term "detection" as used herein, inspection, measurement, detection or can be substituted by the term decision support. Also, the term "evaluation" herein is used in its sense including to help diagnose or evaluated based on the inspection results or measurement results.
[0074]
"Subject" as used herein includes humans, primates, including chimpanzees, dogs, pet animals such as cats, cows, horses, sheep, farm animals such as goats, rodents such as mice, rats, It refers to a mammal, such as animals kept in zoos. A preferred subject is a human. Herein, the term "subject", if by some may be referred to as a "subject". Also, "healthy person" is also, even in such a mammal, means an animal or a subject not suffering from a cancer to be detected. Preferred healthy person is a human.
[0075]
"Ovarian cancer" as used herein includes malignant tumors arising in the ovaries, for example, epithelial ovarian cancer arising from the mucosal epithelium, the germ cell interstitial ovarian cancer.
[0076]
"Ovarian benign tumor" as used herein is a benign tumor that occurs ovary include, for example mucinous cystadenoma, serous cystadenoma, mature teratoma, a fibroma.
[0077]
"Ovarian Tumor", as used herein, is a term that encompasses said that "ovarian cancer" and "ovarian benign tumor".
[0078]
Probability used "P" or "P-value" in the statistical test, the extreme statistic is observed than statistics calculated from actual data under the null hypothesis herein It is shown. Therefore the more "P" or "P-value" is small, considered that there are significant differences between the comparison.
[0079]
As used herein, "sensitivity" means the value of (number of true positives) / (Number of Number + false negatives of true positive). Sensitivity becomes possible to find ovarian cancer early is higher, leading to a decrease in full cancers of resection and recurrence rate.
[0080]
As used herein, "specificity" refers to the (number of true negatives) / (Number of Number + false positives true negatives). If the higher specificity of a healthy person to prevent the implementation of the wasteful additional testing due to misjudged and ovarian cancer patients, leading to a reduction of mitigation and medical expenses of a patient's burden.
[0081]
As used herein, "accuracy" means the value of (the number of number + true negative true positives) / (total number of cases). Accuracy shows the percentage determination result is correct with respect to all the samples, the first indicator for evaluating the detection performance.
[0082]
Determined in the present specification, the detection or diagnosis subject to the "analyte", the occurrence of ovarian cancer, advanced ovarian cancer, and the gene of the present invention is expressed varies with the exertion of the therapeutic effect against ovarian cancer tissues and refers to biological material. Specifically, ovarian tissue and fallopian tubes, the lymph nodes and peripheral organs, also organ metastasis is suspected, skin, and blood, urine, saliva, sweat, body fluids such as tissue exudate, sera prepared from the blood, plasma, other, feces, hair and pointed. Furthermore the biological sample, specifically extracted from these refers to a gene, such as RNA or miRNA.
[0083]
The term is used herein, "hsa-miR-4675 gene" or "hsa-miR-4675" is, hsa-miR-4675 gene described in SEQ ID NO: 1 (miRBase Accession No.MIMAT0019757) and other species such homologue or orthologs are included. hsa-miR-4675 gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4675" takes a hairpin-like structure "hsa-mir-4675" (miRBase Accession No.MI0017306, SEQ ID NO: 276) is known as its precursor.
[0084]
The term is used herein, "hsa-miR-4783-3p gene" or "hsa-miR-4783-3p" is, hsa-miR-4783-3p gene (miRBase Accession described in SEQ ID NO: 2 No. MIMAT0019947), etc. and other species homologs or orthologs are included. hsa-miR-4783-3p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4783-3p" takes a hairpin-like structure "hsa-mir-4783" (miRBase Accession No.MI0017428, SEQ ID NO: 277) is known as its precursor.
[0085]
The term is used herein, "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" is, hsa-miR-1228-5p gene (miRBase Accession described in SEQ ID NO: 3 No. MIMAT0005582), etc. and other species homologs or orthologs are included. hsa-miR-1228-5p gene, Berezikov E et al., 2007, Mol Cell, 28 vol, may be obtained by the method described in P328-336. Further, "hsa-miR-1228-5p" takes a hairpin-like structure "hsa-mir-1228" (miRBase Accession No.MI0006318, SEQ ID NO: 278) is known as its precursor.
[0086]
The term is used herein, "hsa-miR-4532 gene" or "hsa-miR-4532" is, hsa-miR-4532 gene described in SEQ ID NO: 4 (miRBase Accession No.MIMAT0019071) and other species such homologue or orthologs are included. hsa-miR-4532 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in E 118-E127. Further, "hsa-miR-4532" takes a hairpin-like structure "hsa-mir-4532" (miRBase Accession No.MI0016899, SEQ ID NO: 279) is known as its precursor.
[0087]
The term is used herein, "hsa-miR-6802-5p gene" or "hsa-miR-6802-5p" is, hsa-miR-6802-5p gene (miRBase Accession described in SEQ ID NO: 5 No. MIMAT0027504), etc. and other species homologs or orthologs are included. hsa-miR-6802-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6802-5p" takes a hairpin-like structure "hsa-mir-6802" (miRBase Accession No.MI0022647, SEQ ID NO: 280) is known as its precursor.
[0088]
The term is used herein, "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" is, hsa-miR-6784-5p gene (miRBase Accession described in SEQ ID NO: 6 No. MIMAT0027468), etc. and other species homologs or orthologs are included. hsa-miR-6784-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6784-5p" takes a hairpin-like structure "hsa-mir-6784" (miRBase Accession No.MI0022629, SEQ ID NO: 281) is known as its precursor.
[0089]
The term is used herein, "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" is, hsa-miR-3940-5p gene (miRBase Accession according to SEQ ID NO: 7 No. MIMAT0019229), etc. and other species homologs or orthologs are included. hsa-miR-3940-5p gene can be obtained Liao JY et al, 2010, PLoS One, 5 vol., by the method described in E10563. In addition, "hsa-miR-3940-5p" takes a hairpin-like structure "hsa-mir-3940" (miRBase Accession No.MI0016597, SEQ ID NO: 282) is known as its precursor.
The term is used herein, "hsa-miR-1307-3p gene" or "hsa-miR-1307-3p" is, hsa-miR-1307-3p gene (miRBase Accession according to SEQ ID NO: 8 No. MIMAT0005951), etc. and other species homologs or orthologs are included. hsa-miR-1307-3p gene, Morin RD et al., 2008, Genome Res, 18 vol, may be obtained by the method described in P610-621. Further, "hsa-miR-1307-3p" takes a hairpin-like structure "hsa-mir-1307" (miRBase Accession No.MI0006444, SEQ ID NO: 283) is known as its precursor.
[0090]
The term is used herein, "hsa-miR-8073 gene" or "hsa-miR-8073" is, hsa-miR-8073 gene described in SEQ ID NO: 9 (miRBase Accession No.MIMAT0031000) and other species such homologue or orthologs are included. hsa-miR-8073 gene, Wang HJ, et al., 2013, Shock, 39 vol, may be obtained by the method described in P480-487. Further, "hsa-miR-8073" takes a hairpin-like structure "hsa-mir-8073" (miRBase Accession No.MI0025909, SEQ ID NO: 284) is known as its precursor.
[0091]
The term is used herein, "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" is, hsa-miR-3184-5p gene (miRBase Accession of SEQ ID NO: 10 No. MIMAT0015064), etc. and other species homologs or orthologs are included. hsa-miR-3184-5p gene, Stark MS et al., 2010, PLoS One, 5 vol, may be obtained by the method described in E9685. Further, "hsa-miR-3184-5p" takes a hairpin-like structure "hsa-mir-3184" (miRBase Accession No.MI0014226, SEQ ID NO: 285) is known as its precursor.
[0092]
The term is used herein, "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" is, hsa-miR-1233-5p gene (miRBase Accession described in SEQ ID NO: 11 No. MIMAT0022943), etc. and other species homologs or orthologs are included. hsa-miR-1233-5p gene, Berezikov E et al., 2007, Mol Cell, 28 vol, may be obtained by the method described in P328-336. In addition, "hsa-miR-1233-5p" takes a hairpin-like structure as its precursor "hsa-mir-1233-1, hsa-mir-1233-2" (miRBase Accession No.MI0006323, MI0015973, SEQ ID NO: 286, 287) are known.
[0093]
The term is used herein, "hsa-miR-6088 gene" or "hsa-miR-6088" is, hsa-miR-6088 gene described in SEQ ID NO: 12 (miRBase Accession No.MIMAT0023713) and other species such homologue or orthologs are included. hsa-miR-6088 gene can be obtained Yoo JK et al., 2012, Stem Cells Dev, 21 vol., by the method described in P2049-2057. In addition, "hsa-miR-6088" takes a hairpin-like structure "hsa-mir-6088" (miRBase Accession No.MI0020365, SEQ ID NO: 288) is known as its precursor.
[0094]
The term is used herein, "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" is, hsa-miR-5195-3p gene (miRBase Accession of SEQ ID NO: 13 No. MIMAT0021127), etc. and other species homologs or orthologs are included. hsa-miR-5195-3p gene can be obtained Schotte D et al., 2011, Leukemia, 25 vol., by the method described in P1389-1399. Further, "hsa-miR-5195-3p" takes a hairpin-like structure "hsa-mir-5195" (miRBase Accession No.MI0018174, SEQ ID NO: 289) is known as its precursor.
[0095]
The term is used herein, "hsa-miR-320b gene" or "hsa-miR-320b" are, hsa-miR-320b gene described in SEQ ID NO: 14 (miRBase Accession No.MIMAT0005792) and other species such homologue or orthologs are included. hsa-miR-320b gene can be obtained Berezikov E et al, 2006, Genome Res, 16 vol., by the method described in P1289-1298. Further, "hsa-miR-320b", the take hairpin-like structure as a precursor "hsa-mir-320b-1, hsa-mir-320b-2" (miRBase Accession No.MI0003776, MI0003839, SEQ ID NO: 290, 291) is known.
[0096]
The term is used herein, "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" is, hsa-miR-4649-5p gene (miRBase Accession described in SEQ ID NO: 15 No. MIMAT0019711), etc. and other species homologs or orthologs are included. hsa-miR-4649-5p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4649-5p" takes a hairpin-like structure "hsa-mir-4649" (miRBase Accession No.MI0017276, SEQ ID NO: 292) is known as its precursor.
[0097]
The term is used herein, "hsa-miR-6800-5p gene" or "hsa-miR-6800-5p" is, hsa-miR-6800-5p gene (miRBase Accession described in SEQ ID NO: 16 No. MIMAT0027500), etc. and other species homologs or orthologs are included. hsa-miR-6800-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. In addition, "hsa-miR-6800-5p" takes a hairpin-like structure "hsa-mir-6800" (miRBase Accession No.MI0022645, SEQ ID NO: 293) is known as its precursor.
[0098]
The term is used herein, "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" is, hsa-miR-1343-3p gene (miRBase Accession described in SEQ ID NO: 17 No. MIMAT0019776), etc. and other species homologs or orthologs are included. hsa-miR-1343-3p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-1343-3p" takes a hairpin-like structure "hsa-mir-1343" (miRBase Accession No.MI0017320, SEQ ID NO: 294) is known as its precursor.
[0099]
The term is used herein, "hsa-miR-4730 gene" or "hsa-miR-4730" is, hsa-miR-4730 gene described in SEQ ID NO: 18 (miRBase Accession No.MIMAT0019852) and other species such homologue or orthologs are included. hsa-miR-4730 gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4730" takes a hairpin-like structure "hsa-mir-4730" (miRBase Accession No.MI0017367, SEQ ID NO: 295) is known as its precursor.
[0100]
The term is used herein, "hsa-miR-6885-5p gene" or "hsa-miR-6885-5p" is, hsa-miR-6885-5p gene (miRBase Accession set forth in SEQ ID NO: 19 No. MIMAT0027670), etc. and other species homologs or orthologs are included. hsa-miR-6885-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6885-5p" takes a hairpin-like structure "hsa-mir-6885" (miRBase Accession No.MI0022732, SEQ ID NO: 296) is known as its precursor.
[0101]
The term is used herein, "hsa-miR-5100 gene" or "hsa-miR-5100" is, hsa-miR-5100 gene described in SEQ ID NO: 20 (miRBase Accession No.MIMAT0022259) and other species such homologue or orthologs are included. hsa-miR-5100 gene can be obtained Tandon M et al., 2012, Oral Dis, 18 vol., by the method described in P127-131. Further, "hsa-miR-5100" takes a hairpin-like structure "hsa-mir-5100" (miRBase Accession No.MI0019116, SEQ ID NO: 297) is known as its precursor.
[0102]
The term is used herein, "hsa-miR-1203 gene" or "hsa-miR-1203" is, hsa-miR-1203 gene described in SEQ ID NO: 21 (miRBase Accession No.MIMAT0005866) and other species such homologue or orthologs are included. hsa-miR-1203 gene, Marton S et al., 2008, Leukemia, 22 vol, may be obtained by the method described in P330-338. Further, "hsa-miR-1203" takes a hairpin-like structure "hsa-mir-1203" (miRBase Accession No.MI0006335, SEQ ID NO: 298) is known as its precursor.
[0103]
The term is used herein, "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" is, hsa-miR-6756-5p gene (miRBase Accession described in SEQ ID NO: 22 No. MIMAT0027412), etc. and other species homologs or orthologs are included. hsa-miR-6756-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6756-5p" takes a hairpin-like structure "hsa-mir-6756" (miRBase Accession No.MI0022601, SEQ ID NO: 299) is known as its precursor.
[0104]
The term is used herein, "hsa-miR-373-5p gene" or "hsa-miR-373-5p" is, hsa-miR-373-5p gene (miRBase Accession described in SEQ ID NO: 23 No. MIMAT0000725), etc. and other species homologs or orthologs are included. hsa-miR-373-5p gene, Suh MR et al., 2004, Dev Biol, 270 vol, may be obtained by the method described in P488-498. Further, "hsa-miR-373-5p" takes a hairpin-like structure "hsa-mir-373" (miRBase Accession No.MI0000781, SEQ ID NO: 300) is known as its precursor.
[0105]
The term is used herein, "hsa-miR-1268a gene" or "hsa-miR-1268a" is, hsa-miR-1268a gene described in SEQ ID NO: 24 (miRBase Accession No.MIMAT0005922) and other species such homologue or orthologs are included. hsa-miR-1268a gene, Morin RD et al., 2008, Genome Res, 18 vol, may be obtained by the method described in P610-621. Further, "hsa-miR-1268a" takes a hairpin-like structure "hsa-mir-1268a" (miRBase Accession No.MI0006405, SEQ ID NO: 301) is known as its precursor.
[0106]
The term is used herein, "hsa-miR-1260b gene" or "hsa-miR-1260b" is, hsa-miR-1260b gene described in SEQ ID NO: 25 (miRBase Accession No.MIMAT0015041) and other species such homologue or orthologs are included. hsa-miR-1260b gene, Stark MS et al., 2010, PLoS One, 5 vol, may be obtained by the method described in E9685. Further, "hsa-miR-1260b" takes a hairpin-like structure "hsa-mir-1260b" (miRBase Accession No.MI0014197, SEQ ID NO: 302) is known as its precursor.
[0107]
The term is used herein, "hsa-miR-4258 gene" or "hsa-miR-4258" is, hsa-miR-4258 gene described in SEQ ID NO: 26 (miRBase Accession No.MIMAT0016879) and other species such homologue or orthologs are included. hsa-miR-4258 gene can be obtained Goff LA et al., 2009, PLoS One, 4 vol., by the method described in E7192. Further, "hsa-miR-4258" takes a hairpin-like structure "hsa-mir-4258" (miRBase Accession No.MI0015857, SEQ ID NO: 303) is known as its precursor.
[0108]
The term is used herein, "hsa-miR-4697-5p gene" or "hsa-miR-4697-5p" is, hsa-miR-4697-5p gene (miRBase Accession described in SEQ ID NO: 27 No. MIMAT0019791), etc. and other species homologs or orthologs are included. hsa-miR-4697-5p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4697-5p" takes a hairpin-like structure "hsa-mir-4697" (miRBase Accession No.MI0017330, SEQ ID NO: 304) is known as its precursor.
[0109]
The term is used herein, "hsa-miR-1469 gene" or "hsa-miR-1469" is, hsa-miR-1469 gene described in SEQ ID NO: 28 (miRBase Accession No.MIMAT0007347) and other species such homologue or orthologs are included. hsa-miR-1469 gene, Kawaji H et al, 2008, BMC Genomics, 9 vol, may be obtained by the method described in P157. Further, "hsa-miR-1469" takes a hairpin-like structure "hsa-mir-1469" (miRBase Accession No.MI0007074, SEQ ID NO: 305) is known as its precursor.
[0110]
The term is used herein, "hsa-miR-4515 gene" or "hsa-miR-4515" is, hsa-miR-4515 gene described in SEQ ID NO: 29 (miRBase Accession No.MIMAT0019052) and other species such homologue or orthologs are included. hsa-miR-4515 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in E 118-E127. Further, "hsa-miR-4515" takes a hairpin-like structure "hsa-mir-4515" (miRBase Accession No.MI0016881, SEQ ID NO: 306) is known as its precursor.
[0111]
The term is used herein, "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" is, hsa-miR-6861-5p gene (miRBase Accession described in SEQ ID NO: 30 No. MIMAT0027623), etc. and other species homologs or orthologs are included. hsa-miR-6861-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6861-5p" takes a hairpin-like structure "hsa-mir-6861" (miRBase Accession No.MI0022708, SEQ ID NO: 307) is known as its precursor.
[0112]
The term is used herein, "hsa-miR-6821-5p gene" or "hsa-miR-6821-5p" is, hsa-miR-6821-5p gene (miRBase Accession described in SEQ ID NO: 31 No. MIMAT0027542), etc. and other species homologs or orthologs are included. hsa-miR-6821-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6821-5p" takes a hairpin-like structure "hsa-mir-6821" (miRBase Accession No.MI0022666, SEQ ID NO: 308) is known as its precursor.
[0113]
The term is used herein, "hsa-miR-575 gene" or "hsa-miR-575" is, hsa-miR-575 gene described in SEQ ID NO: 32 (miRBase Accession No.MIMAT0003240) and other species such homologue or orthologs are included. hsa-miR-575 gene, Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103 vol, may be obtained by the method described in P3687-3692. Further, "hsa-miR-575" takes a hairpin-like structure "hsa-mir-575" (miRBase Accession No.MI0003582, SEQ ID NO: 309) is known as its precursor.
[0114]
The term is used herein, "hsa-miR-6805-5p gene" or "hsa-miR-6805-5p" is, hsa-miR-6805-5p gene (miRBase Accession described in SEQ ID NO: 33 No. MIMAT0027510), etc. and other species homologs or orthologs are included. hsa-miR-6805-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6805-5p" takes a hairpin-like structure "hsa-mir-6805" (miRBase Accession No.MI0022650, SEQ ID NO: 310) is known as its precursor.
[0115]
The term is used herein, "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" is, hsa-miR-4758-5p gene (miRBase Accession described in SEQ ID NO: 34 No. MIMAT0019903), etc. and other species homologs or orthologs are included. hsa-miR-4758-5p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4758-5p" takes a hairpin-like structure "hsa-mir-4758" (miRBase Accession No.MI0017399, SEQ ID NO: 311) is known as its precursor.
[0116]
The term is used herein, "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" is, hsa-miR-3663-3p gene (miRBase Accession described in SEQ ID NO: 35 No. MIMAT0018085), etc. and other species homologs or orthologs are included. hsa-miR-3663-3p gene can be obtained Liao JY et al, 2010, PLoS One, 5 vol., by the method described in E10563. Further, "hsa-miR-3663-3p" takes a hairpin-like structure "hsa-mir-3663" (miRBase Accession No.MI0016064, SEQ ID NO: 312) is known as its precursor.
[0117]
The term is used herein, "hsa-miR-4530 gene" or "hsa-miR-4530" is, hsa-miR-4530 gene described in SEQ ID NO: 36 (miRBase Accession No.MIMAT0019069) and other species such homologue or orthologs are included. hsa-miR-4530 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in E 118-E127. Further, "hsa-miR-4530" takes a hairpin-like structure "hsa-mir-4530" (miRBase Accession No.MI0016897, SEQ ID NO: 313) is known as its precursor.
[0118]
The term is used herein, "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" is, hsa-miR-6798-5p gene (miRBase Accession shown in SEQ ID NO: 37 No. MIMAT0027496), etc. and other species homologs or orthologs are included. hsa-miR-6798-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6798-5p" takes a hairpin-like structure "hsa-mir-6798" (miRBase Accession No.MI0022643, SEQ ID NO: 314) is known as its precursor.
[0119]
The term is used herein, "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" is, hsa-miR-6781-5p gene (miRBase Accession set forth in SEQ ID NO: 38 No. MIMAT0027462), etc. and other species homologs or orthologs are included. hsa-miR-6781-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6781-5p" takes a hairpin-like structure "hsa-mir-6781" (miRBase Accession No.MI0022626, SEQ ID NO: 315) is known as its precursor.
[0120]
The term is used herein, "hsa-miR-885-3p gene" or "hsa-miR-885-3p" is, hsa-miR-885-3p gene (miRBase Accession forth in SEQ ID NO: 39 No. MIMAT0004948), etc. and other species homologs or orthologs are included. hsa-miR-885-3p gene can be obtained Berezikov E et al, 2006, Genome Res, 16 vol., by the method described in P1289-1298. Further, "hsa-miR-885-3p" takes a hairpin-like structure "hsa-mir-885" (miRBase Accession No.MI0005560, SEQ ID NO: 316) is known as its precursor.
[0121]
The term is used herein, "hsa-miR-1273g-3p gene" or "hsa-miR-1273g-3p" is, hsa-miR-1273g-3p gene described in SEQ ID NO: 40 (miRBase Accession No. MIMAT0022742), etc. and other species homologs or orthologs are included. hsa-miR-1273g-3p gene can be obtained Reshmi G et al., 2011, Genomics, 97, pp. by the method described in P333-340. Further, "hsa-miR-1273g-3p" takes a hairpin-like structure "hsa-mir-1273g" (miRBase Accession No.MI0018003, SEQ ID NO: 317) is known as its precursor.
[0122]
The term is used herein, "hsa-miR-4787-3p gene" or "hsa-miR-4787-3p" is, hsa-miR-4787-3p gene (miRBase Accession described in SEQ ID NO: 41 No. MIMAT0019957), etc. and other species homologs or orthologs are included. hsa-miR-4787-3p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4787-3p" takes a hairpin-like structure "hsa-mir-4787" (miRBase Accession No.MI0017434, SEQ ID NO: 318) is known as its precursor.
[0123]
The term is used herein, "hsa-miR-4454 gene" or "hsa-miR-4454" is, hsa-miR-4454 gene described in SEQ ID NO: 42 (miRBase Accession No.MIMAT0018976) and other species such homologue or orthologs are included. hsa-miR-4454 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in E 118-E127. Further, "hsa-miR-4454" takes a hairpin-like structure "hsa-mir-4454" (miRBase Accession No.MI0016800, SEQ ID NO: 319) is known as its precursor.
[0124]
The term is used herein, "hsa-miR-4706 gene" or "hsa-miR-4706" is, hsa-miR-4706 gene described in SEQ ID NO: 43 (miRBase Accession No.MIMAT0019806) and other species such homologue or orthologs are included. hsa-miR-4706 gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4706" takes a hairpin-like structure "hsa-mir-4706" (miRBase Accession No.MI0017339, SEQ ID NO: 320) is known as its precursor.
[0125]
The term is used herein, "hsa-miR-1249-3p gene" or "hsa-miR-1249-3p" is, hsa-miR-1249-3p gene (miRBase Accession described in SEQ ID NO: 44 No. MIMAT0005901), etc. and other species homologs or orthologs are included. hsa-miR-1249-3p gene, Morin RD et al., 2008, Genome Res, 18 vol, may be obtained by the method described in P610-621. Further, "hsa-miR-1249-3p" takes a hairpin-like structure "hsa-mir-1249" (miRBase Accession No.MI0006384, SEQ ID NO: 321) is known as its precursor.
[0126]
The term is used herein, "hsa-miR-887-3p gene" or "hsa-miR-887-3p" is, hsa-miR-887-3p gene (miRBase Accession set forth in SEQ ID NO: 45 No. MIMAT0004951), etc. and other species homologs or orthologs are included. hsa-miR-887-3p gene can be obtained Berezikov E et al, 2006, Genome Res, 16 vol., by the method described in P1289-1298. Further, "hsa-miR-887-3p" takes a hairpin-like structure "hsa-mir-887" (miRBase Accession No.MI0005562, SEQ ID NO: 322) is known as its precursor.
[0127]
The term is used herein, "hsa-miR-6786-5p gene" or "hsa-miR-6786-5p" is, hsa-miR-6786-5p gene (miRBase Accession described in SEQ ID NO: 46 No. MIMAT0027472), etc. and other species homologs or orthologs are included. hsa-miR-6786-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6786-5p" takes a hairpin-like structure "hsa-mir-6786" (miRBase Accession No.MI0022631, SEQ ID NO: 323) is known as its precursor.
[0128]
The term is used herein, "hsa-miR-1238-5p gene" or "hsa-miR-1238-5p" is, hsa-miR-1238-5p gene (miRBase Accession described in SEQ ID NO: 47 No. MIMAT0022947), etc. and other species homologs or orthologs are included. hsa-miR-1238-5p gene, Berezikov E et al., 2007, Mol Cell, 28 vol, may be obtained by the method described in P328-336. Further, "hsa-miR-1238-5p" takes a hairpin-like structure "hsa-mir-1238" (miRBase Accession No.MI0006328, SEQ ID NO: 324) is known as its precursor.
[0129]
The term is used herein, "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" is, hsa-miR-6749-5p gene (miRBase Accession described in SEQ ID NO: 48 No. MIMAT0027398), etc. and other species homologs or orthologs are included. hsa-miR-6749-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6749-5p" takes a hairpin-like structure "hsa-mir-6749" (miRBase Accession No.MI0022594, SEQ ID NO: 325) is known as its precursor.
[0130]
The term is used herein, "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" is, hsa-miR-6729-5p gene (miRBase Accession described in SEQ ID NO: 49 No. MIMAT0027359), etc. and other species homologs or orthologs are included. hsa-miR-6729-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6729-5p" takes a hairpin-like structure "hsa-mir-6729" (miRBase Accession No.MI0022574, SEQ ID NO: 326) is known as its precursor.
[0131]
The term is used herein, "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" is, hsa-miR-6825-5p gene (miRBase Accession set forth in SEQ ID NO: 50 No. MIMAT0027550), etc. and other species homologs or orthologs are included. hsa-miR-6825-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6825-5p" takes a hairpin-like structure "hsa-mir-6825" (miRBase Accession No.MI0022670, SEQ ID NO: 327) is known as its precursor.
[0132]
The term is used herein, "hsa-miR-663b gene" or "hsa-miR-663b" are, hsa-miR-663b gene described in SEQ ID NO: 51 (miRBase Accession No.MIMAT0005867) and other species such homologue or orthologs are included. hsa-miR-663b gene, Takada S, et al., 2008, Leukemia, 22 vol, may be obtained by the method described in P1274-1278. Further, "hsa-miR-663b" takes a hairpin-like structure "hsa-mir-663b" (miRBase Accession No.MI0006336, SEQ ID NO: 328) is known as its precursor.
[0133]
The term is used herein, "hsa-miR-6858-5p gene" or "hsa-miR-6858-5p" is, hsa-miR-6858-5p gene (miRBase Accession described in SEQ ID NO: 52 No. MIMAT0027616), etc. and other species homologs or orthologs are included. hsa-miR-6858-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6858-5p" takes a hairpin-like structure "hsa-mir-6858" (miRBase Accession No.MI0022704, SEQ ID NO: 329) is known as its precursor.
[0134]
The term is used herein, "hsa-miR-4690-5p gene" or "hsa-miR-4690-5p" is, hsa-miR-4690-5p gene (miRBase Accession described in SEQ ID NO: 53 No. MIMAT0019779), etc. and other species homologs or orthologs are included. hsa-miR-4690-5p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4690-5p" takes a hairpin-like structure "hsa-mir-4690" (miRBase Accession No.MI0017323, SEQ ID NO: 330) is known as its precursor.
[0135]
The term is used herein, "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" is, hsa-miR-6765-5p gene (miRBase Accession described in SEQ ID NO: 54 No. MIMAT0027430), etc. and other species homologs or orthologs are included. hsa-miR-6765-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6765-5p" takes a hairpin-like structure "hsa-mir-6765" (miRBase Accession No.MI0022610, SEQ ID NO: 331) is known as its precursor.
[0136]
The term is used herein, "hsa-miR-4710 gene" or "hsa-miR-4710" is, hsa-miR-4710 gene described in SEQ ID NO: 55 (miRBase Accession No.MIMAT0019815) and other species such homologue or orthologs are included. hsa-miR-4710 gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. In addition, "hsa-miR-4710" takes a hairpin-like structure "hsa-mir-4710" (miRBase Accession No.MI0017344, SEQ ID NO: 332) is known as its precursor.
[0137]
The term is used herein, "hsa-miR-6775-5p gene" or "hsa-miR-6775-5p" is, hsa-miR-6775-5p gene (miRBase Accession described in SEQ ID NO: 56 No. MIMAT0027450), etc. and other species homologs or orthologs are included. hsa-miR-6775-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6775-5p" takes a hairpin-like structure "hsa-mir-6775" (miRBase Accession No.MI0022620, SEQ ID NO: 333) is known as its precursor.
[0138]
The term is used herein, "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" is, hsa-miR-371a-5p gene described in SEQ ID NO: 57 (miRBase Accession No. MIMAT0004687), etc. and other species homologs or orthologs are included. hsa-miR-371a-5p gene, Suh MR et al., 2004, Dev Biol, 270 vol, may be obtained by the method described in P488-498. In addition, "hsa-miR-371a-5p" takes a hairpin-like structure "hsa-mir-371a" (miRBase Accession No.MI0000779, SEQ ID NO: 334) is known as its precursor.
[0139]
The term is used herein, "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" is, hsa-miR-6816-5p gene (miRBase Accession described in SEQ ID NO: 58 No. MIMAT0027532), etc. and other species homologs or orthologs are included. hsa-miR-6816-5p gene can be obtained Ladewig E et al, 2012, Genome Res, 22 vol., by the method described in P1634-1645. Further, "hsa-miR-6816-5p" takes a hairpin-like structure "hsa-mir-6816" (miRBase Accession No.MI0022661, SEQ ID NO: 335) is known as its precursor.
[0140]
The term is used herein, "hsa-miR-296-3p gene" or "hsa-miR-296-3p" is, hsa-miR-296-3p gene (miRBase Accession described in SEQ ID NO: 59 No. MIMAT0004679), etc. and other species homologs or orthologs are included. hsa-miR-296-3p gene, Houbaviy HB et al., 2003, Dev Cell, 5 vol, may be obtained by the method described in P351-358. Further, "hsa-miR-296-3p" takes a hairpin-like structure "hsa-mir-296" (miRBase Accession No.MI0000747, SEQ ID NO: 336) is known as its precursor.
[0141]
The term is used herein, "hsa-miR-7977 gene" or "hsa-miR-7977" is, hsa-miR-7977 gene described in SEQ ID NO: 60 (miRBase Accession No.MIMAT0031180) and other species such homologue or orthologs are included. hsa-miR-7977 gene can be obtained Velthut-Meikas A et al, 2013, Mol Endocrinol, 27 vol., by the method described in P1128-1141. Further, "hsa-miR-7977" takes a hairpin-like structure "hsa-mir-7977" (miRBase Accession No.MI0025753, SEQ ID NO: 337) is known as its precursor.
[0142]
The term is used herein, "hsa-miR-8069 gene" or "hsa-miR-8069" is, hsa-miR-8069 gene described in SEQ ID NO: 61 (miRBase Accession No.MIMAT0030996) and other species such homologue or orthologs are included. hsa-miR-8069 gene, Wang HJ, et al., 2013, Shock, 39 vol, may be obtained by the method described in P480-487. In addition, "hsa-miR-8069" takes a hairpin-like structure as its precursor "hsa-mir-8069-1, hsa-mir-8069-2" (miRBase Accession No.MI0025905, MI0031519, SEQ ID NO: 338, 339) is known.
[0143]
The term is used herein, "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" is, hsa-miR-6515-3p gene (miRBase Accession described in SEQ ID NO: 62 No. MIMAT0025487), etc. and other species homologs or orthologs are included. hsa-miR-6515-3p gene, Joyce CE et al, 2011, Hum Mol Genet, 20 vol, may be obtained by the method described in P4025-4040. Further, "hsa-miR-6515-3p" takes a hairpin-like structure "hsa-mir-6515" (miRBase Accession No.MI0022227, SEQ ID NO: 340) is known as its precursor.
[0144]
The term is used herein, "hsa-miR-4687-5p gene" or "hsa-miR-4687-5p" is, hsa-miR-4687-5p gene (miRBase Accession described in SEQ ID NO: 63 No. MIMAT0019774), etc. and other species homologs or orthologs are included. hsa-miR-4687-5p gene can be obtained Persson H, et al., 2011, Cancer Res, 71 vol., by the method described in P78-86. Further, "hsa-miR-4687-5p" takes a hairpin-like structure "hsa-mir-4687" (miRBase Accession No.MI0017319, SEQ ID NO: 341) is known as its precursor.
claims:-
[Requested item 1]
miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307-3p, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p, miR 4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, 1260b-miR, miR-4258, miR-4697-5p, miR-1469, miR-4515, miR-6861-5p miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885-3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749-5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a-5p, miR-6816-5p, miR-296-3p, miR-7 77, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR-614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR-1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR 6766-3p, miR-197-5p, miR-6887- 5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR 6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR-6840- 3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR 3648, miR-4732-5p, miR-47 7-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR 6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR 4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p, miR-4433a-3p, miR-4274, miR 419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR-4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR 6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722-5p, miR-4746-3p, miR-4450, miR-6 795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR 6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671-5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR-6763- 5p, miR-1908-3p, miR-1181, miR 6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR-4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR-3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR 6791-5p, miR-6819-5 , MiR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p
[Requested item 2]
Said nucleic acid, a polynucleotide shown in any one of the following (a) -
(e): (a) u In the nucleotide sequence or the nucleotide sequence shown in any of SEQ ID NO: 1 to 247,251 and 268 t a polynucleotide consisting of the nucleotide sequence is, the variant, derivative, or fragment thereof comprising 15 or more continuous nucleotides,
a nucleotide sequence represented by any one of (b) SEQ ID NO: 1 to 247,251 and 268 polynucleotide, comprising
(c) SEQ ID NO: 1 to 247,251 and u in the nucleotide sequence or the nucleotide sequence shown in any of 268 consisting of a nucleotide sequence complementary to the nucleotide sequence is t polynucleotide variants body, its derivative, or fragment thereof comprising 15 or more contiguous
bases, base represented by any one of (d) SEQ ID NO: 1 to 247,251 and 268 Polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the sequence or the nucleotide sequence, and
(e) wherein (a) hybridizes under any of the polynucleotides under stringent conditions of ~ (d) polynucleotide to
a polynucleotide selected from the group consisting of a kit according to claim 1.
[Requested item 3]
The kit is another ovarian tumor marker, miR-320a, miR-663a, miR-328-5p, miR-128-2-5p, miR-125a-3p, miR-191-5p, miR-92b- 5p, miR-296-5p, miR-1246, miR-92a-2-5p, miR-128-1-5p, miR-1290, miR-211-3p, miR-744-5p, miR-135a-3p, miR-451a, miR-625-3p, miR-92a-3p, miR-422a, miR-483-5p, miR-652-5p, miR-24-3p, miR-23b-3p, miR-23a-3p, miR-92b-3p, at least one polynucleotide selected from miR-22-3p, or the Porinukure Further comprising a complementary strand capable of specifically binding a nucleic acid of the tides, the kit according to claim 1 or 2.
[Requested item 4]
Said nucleic acid, a polynucleotide shown in any one of the following (f) -
(j): (f) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ nucleotide sequence or the nucleotide sequence shown in any of 275 a polynucleotide consisting of the nucleotide sequence u is t in, a variant, derivative, or fragment thereof comprising 15 or more continuous
nucleotides, either (g) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 a polynucleotide comprising the nucleotide sequence represented by
either the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (h) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 polynucleotide comprising a nucleotide sequence complementary, the fragment comprising the variant, derivative, or 15 or more continuous nucleotides,
(i) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence shown in any of 275, and
(j) the (f) any of the polynucleotides under stringent conditions with a polynucleotide hybridizing of ~ (i),
a polynucleotide selected from the group consisting of a kit according to claim 3.
[Requested item 5]
miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307-3p, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p, miR 4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, 1260b-miR, miR-4258, miR-4697-5p, miR-1469, miR-4515, miR-6861-5p miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885-3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749-5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a-5p, miR-6816-5p, miR-296-3p, miR-7 77, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR-614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR-1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR 6766-3p, miR-197-5p, miR-6887- 5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR 6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR-6840- 3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR 3648, miR-4732-5p, miR-47 7-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR 6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR 4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p, miR-4433a-3p, miR-4274, miR 419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR-4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR 6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722-5p, miR-4746-3p, miR-4450, miR-6 795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR 6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671-5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR-6763- 5p, miR-1908-3p, miR-1181, miR 6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR-4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR-3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR 6791-5p, miR-6819-5 , MiR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p 及 び miR-642a-3p
[Requested item 6]
Said nucleic acid, a polynucleotide shown in any one of the following (a) -
(e): (a) u In the nucleotide sequence or the nucleotide sequence shown in any of SEQ ID NO: 1 to 247,251 and 268 t a polynucleotide consisting of the nucleotide sequence is, the variant, derivative, or fragment thereof comprising 15 or more continuous nucleotides,
a nucleotide sequence represented by any one of (b) SEQ ID NO: 1 to 247,251 and 268 polynucleotide, comprising
(c) SEQ ID NO: 1 to 247,251 and u in the nucleotide sequence or the nucleotide sequence shown in any of 268 consisting of a nucleotide sequence complementary to the nucleotide sequence is t polynucleotide variants body, its derivative, or fragment thereof comprising 15 or more contiguous
bases, base represented by any one of (d) SEQ ID NO: 1 to 247,251 and 268 Polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the sequence or the nucleotide sequence, and
(e) wherein (a) hybridizes under any of the polynucleotides under stringent conditions of ~ (d) polynucleotide,
a polynucleotide selected from the group consisting of a device according to claim 5.
[Requested item 7]
It said device is another ovarian tumor marker, miR-320a, miR-663a, miR-328-5p, miR-128-2-5p, miR-125a-3p, miR-191-5p, miR-92b- 5p, miR-296-5p, miR-1246, miR-92a-2-5p, miR-128-1-5p, miR-1290, miR-211-3p, miR-744-5p, miR-135a-3p, miR-451a, miR-625-3p, miR-92a-3p, miR-422a, miR-483-5p, miR-652-5p, miR-24-3p, miR-23b-3p, miR-23a-3p, miR-92b-3p, at least one polynucleotide selected from miR-22-3p, or the Porinuku Further comprising a complementary strand capable of specifically binding a nucleic acid of the fault, device according to claim 5 or 6.
[Requested item 8]
Said nucleic acid, a polynucleotide shown in any one of the following (f) -
(j): (f) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ nucleotide sequence or the nucleotide sequence shown in any of 275 a polynucleotide consisting of the nucleotide sequence u is t in, a variant, derivative, or fragment thereof comprising 15 or more continuous
nucleotides, either (g) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 a polynucleotide comprising the nucleotide sequence represented by
either the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (h) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 polynucleotide comprising a nucleotide sequence complementary, the fragment comprising the variant, derivative, or 15 or more continuous nucleotides,
(i) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence shown in any of 275, and
(j) the (f) any of the polynucleotides under stringent conditions with a polynucleotide hybridizing of ~ (i),
a polynucleotide selected from the group consisting of, according to claim 7 device.
[Requested item 9]
It said device is a device for the measurement by hybridization techniques, according to any one of claims 5-8 device.
[Requested item 10]
The hybridization techniques, a nucleic acid array technology, according to claim 9 device.
[Requested item 11]
The sample of the subject, ovarian tumor marker, miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307-3p, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR- 1343-3p, miR-4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, miR-1260b, miR-4258, miR-4697- 5p, miR-1469, miR-4515, iR-6861-5p, miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885-3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749-5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a-5p, miR-6816-5p, miR-2 6-3p, miR-7977, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787- 5p, miR-614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757- 5p, miR-1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR-6766-3p, miR-197-5 p, miR-6887-5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR- 1225-3p, miR-6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR- 4429, miR-6840-3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR-3648, miR-473 -5p, miR-4787-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114 -5p, miR-6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a -5p, miR-4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR -1229-5p, miR-4433a-3p, mi -4274, miR-4419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p , miR-4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108 -3p, miR-6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR -4722-5p, miR-4746-3p, miR -4450, miR-6795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a -5p, miR-6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR -671-5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p , miR-6763-5p, miR-1908-3p, m R-1181, miR-6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR- 4259, miR-4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771- 5p, miR-3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR- 6732-5p, miR-6791-5p miR-6819-5p, miR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p, the expression level of at least one polynucleotide selected from miR-642a-3p measured includes evaluating the subject using the expression amount is the measurement is afflicted with ovarian tumors, or not to be suffering from ovarian tumor in vitro, the detection method of ovarian tumors.
[Requested item 12]
miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307-3p, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p, miR 4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, 1260b-miR, miR-4258, miR-4697-5p, miR-1469, miR-4515, miR-6861-5p miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885-3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749-5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a-5p, miR-6816-5p, miR-296-3p, miR-7 77, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR-614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR-1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR 6766-3p, miR-197-5p, miR-6887- 5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR 6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR-6840- 3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR 3648, miR-4732-5p, miR-47 7-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR 6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR 4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p, miR-4433a-3p, miR-4274, miR 419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR-4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR 6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722-5p, miR-4746-3p, miR-4450, miR-6 795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR 6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671-5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR-6763- 5p, miR-1908-3p, miR-1181, miR 6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR-4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR-3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR 6791-5p, miR-6819-5 , MiR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p, miR-642a-3p
[Requested item 13]
miR-4675, miR-4783-3p, miR-1228-5p, miR-4532, miR-6802-5p, miR-6784-5p, miR-3940-5p, miR-1307-3p, miR-8073, miR-3184-5p, miR-1233-5p, miR-6088, miR-5195-3p, miR-320b, miR-4649-5p, miR-6800-5p, miR-1343-3p, miR 4730, miR-6885-5p, miR-5100, miR-1203, miR-6756-5p, miR-373-5p, miR-1268a, 1260b-miR, miR-4258, miR-4697-5p, miR-1469, miR-4515, miR-6861-5p miR-6821-5p, miR-575, miR-6805-5p, miR-4758-5p, miR-3663-3p, miR-4530, miR-6798-5p, miR-6781-5p, miR-885-3p, miR-1273g-3p, miR-4787-3p, miR-4454, miR-4706, miR-1249-3p, miR-887-3p, miR-6786-5p, miR-1238-5p, miR-6749-5p, miR-6729-5p, miR-6825-5p, miR-663b, miR-6858-5p, miR-4690-5p, miR-6765-5p, miR-4710, miR-6775-5p, miR-371a-5p, miR-6816-5p, miR-296-3p, miR-7 77, miR-8069, miR-6515-3p, miR-4687-5p, miR-1343-5p, miR-7110-5p, miR-4525, miR-3158-5p, miR-6787-5p, miR-614, miR-4689, miR-1185-2-3p, miR-1268b, miR-1228-3p, miR-1185-1-3p, miR-940, miR-939-5p, miR-6757-5p, miR-1275, miR-5001-5p, miR-6826-5p, miR-6765-3p, miR-3679-3p, miR-4718, miR-4286, miR-8059, miR-4447, miR-4448, miR-658, miR 6766-3p, miR-197-5p, miR-6887- 5p, miR-6742-5p, miR-6729-3p, miR-5090, miR-7975, miR-4505, miR-6889-5p, miR-4708-3p, miR-6131, miR-1225-3p, miR 6132, miR-4734, miR-3194-3p, miR-638, miR-2467-3p, miR-4728-5p, miR-5572, miR-6789-5p, miR-8063, miR-4429, miR-6840- 3p, miR-4476, miR-675-5p, miR-711, miR-6875-5p, miR-3160-5p, miR-1908-5p, miR-6726-5p, miR-1913, miR-8071, miR 3648, miR-4732-5p, miR-47 7-5p, miR-3917, miR-619-5p, miR-1231, miR-342-5p, miR-4433a-5p, miR-6766-5p, miR-4707-5p, miR-7114-5p, miR 6872-3p, miR-6780b-5p, miR-7845-5p, miR-6798-3p, miR-665, miR-6848-5p, miR-5008-5p, miR-4294, miR-6511a-5p, miR 4435, miR-4747-3p, miR-6880-3p, miR-6869-5p, miR-7150, miR-1260a, miR-6877-5p, miR-6721-5p, miR-4656, miR-1229-5p, miR-4433a-3p, miR-4274, miR 419b, miR-4674, miR-6893-5p, miR-6763-3p, miR-6762-5p, miR-6738-5p, miR-4513, miR-6746-5p, miR-6880-5p, miR-4736, miR-718, miR-6717-5p, miR-7847-3p, miR-760, miR-1199-5p, miR-6813-5p, miR-6769a-5p, miR-1193, miR-7108-3p, miR 6741-5p, miR-4298, miR-6796-3p, miR-4750-5p, miR-6785-5p, miR-1292-3p, miR-4749-3p, miR-6800-3p, miR-4722-5p, miR-4746-3p, miR-4450, miR-6 795-5p, miR-365a-5p, miR-498, miR-6797-5p, miR-1470, miR-6851-5p, miR-1247-3p, miR-5196-5p, miR-208a-5p, miR 6842-5p, miR-150-3p, miR-4534, miR-3135b, miR-3131, miR-4792, miR-6510-5p, miR-504-3p, miR-3619-3p, miR-671-5p, miR-4667-5p, miR-4430, miR-3195, miR-3679-5p, miR-6076, miR-6515-5p, miR-6820-5p, miR-4634, miR-187-5p, miR-6763- 5p, miR-1908-3p, miR-1181, miR 6782-5p, miR-5010-5p, miR-6870-5p, miR-6124, miR-1249-5p, miR-6511b-5p, miR-1254, miR-4727-3p, miR-4259, miR-4771, miR-3622a-5p, miR-4480, miR-4740-5p, miR-6777-5p, miR-6794-5p, miR-4687-3p, miR-6743-5p, miR-6771-5p, miR-3141, miR-3162-5p, miR-4271, miR-1227-5p, miR-4257, miR-4270, miR-4516, miR-4651, miR-4725-3p, miR-6125, miR-6732-5p, miR 6791-5p, miR-6819-5 , MiR-6891-5p, miR-7108-5p, miR-7109-5p, miR-642b-3p, miR-642a-3p
[Requested item 14]
Said nucleic acid, a polynucleotide shown in any one of the following (a) -
(e): is u in (a) nucleotide sequence shown in any of SEQ ID NO: 1 to 247,251 and 268, or the nucleotide sequence nucleotide sequence is t, a polynucleotide consisting of a variant, derivative, or fragment thereof comprising 15 or more contiguous
bases, base represented by any one of (b) SEQ ID NO: 1 to 247,251 and 268 polynucleotide comprising a sequence
consisting of the nucleotide sequence, a complementary nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (c) SEQ ID NO: 1 to 247,251 and 268 poly nucleotides, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous
nucleotides, represented by any of (d) SEQ ID NO: 1 to 247,251 and 268 Nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence, to a polynucleotide comprising a complementary base sequence and
a any polynucleotide stringent in (e) above (a) ~ (d) conditions hybridizing polynucleotide, with
a polynucleotide selected from the group consisting of a method according to any one of claims 11 to 13.
[Requested item 15]
The kit or device is another ovarian tumor marker, miR-320a, miR-663a, miR-328-5p, miR-128-2-5p, miR-125a-3p, miR-191-5p, miR- 92b-5p, miR-296-5p, miR-1246, miR-92a-2-5p, miR-128-1-5p, miR-1290, miR-211-3p, miR-744-5p, miR-135a- 3p, miR-451a, miR-625-3p, miR-92a-3p, miR-422a, miR-483-5p, miR-652-5p, miR-24-3p, miR-23b-3p, miR-23a- 3p, miR-92b-3p, at least one polynucleotide selected from miR-22-3p, or Further comprising a complementary strand capable of specifically binding a nucleic acid of the polynucleotide, the method according to any one of claims 11 to 14.
[Requested item 16]
Said nucleic acid, a polynucleotide shown in any one of the following (f) -
(j): (f) the nucleotide sequence shown in any of SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269-275, or the base nucleotide sequence, a polynucleotide consisting of u is t in the sequence, a variant thereof, a fragment comprising the derivative, or 15 or more continuous
nucleotides, (g) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275
polynucleotides the u in the nucleotide sequence or the nucleotide sequence represented by any one of (h) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 to 275 is t a polynucleotide consisting of the nucleotide sequence, a complementary nucleotide sequence, the fragment comprising the variant, derivative, or 15 or more contiguous bases
(I) SEQ ID NO: 248 ~ 250, 252 ~ 267 and 269 ~ polynucleotide comprising a nucleotide sequence, a complementary nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence shown in any of 275, and
(j) wherein (f) ~ any polynucleotide and a polynucleotide hybridizing under stringent conditions (i),
a polynucleotide selected from the group consisting of the method of claim 15.
[Requested item 17]
Wherein the subject is a human, the method according to any one of claims 11 to 16.
[Requested item 18]
Wherein the analyte is blood, serum or plasma, the method according to any one of claims 11 to 17.
| # | Name | Date |
|---|---|---|
| 1 | 201937047926-STATEMENT OF UNDERTAKING (FORM 3) [23-11-2019(online)].pdf | 2019-11-23 |
| 2 | 201937047926-SEQUENCE LISTING(PDF) [23-11-2019(online)].pdf | 2019-11-23 |
| 3 | 201937047926-SEQUENCE LISTING [23-11-2019(online)].txt | 2019-11-23 |
| 4 | 201937047926-PROOF OF RIGHT [23-11-2019(online)].pdf | 2019-11-23 |
| 5 | 201937047926-POWER OF AUTHORITY [23-11-2019(online)].pdf | 2019-11-23 |
| 6 | 201937047926-NOTIFICATION OF INT. APPLN. NO. & FILING DATE (PCT-RO-105) [23-11-2019(online)].pdf | 2019-11-23 |
| 7 | 201937047926-FORM 1 [23-11-2019(online)].pdf | 2019-11-23 |
| 8 | 201937047926-FIGURE OF ABSTRACT [23-11-2019(online)].pdf | 2019-11-23 |
| 9 | 201937047926-DRAWINGS [23-11-2019(online)].pdf | 2019-11-23 |
| 10 | 201937047926-DECLARATION OF INVENTORSHIP (FORM 5) [23-11-2019(online)].pdf | 2019-11-23 |
| 11 | 201937047926-COMPLETE SPECIFICATION [23-11-2019(online)].pdf | 2019-11-23 |
| 12 | 201937047926.pdf | 2019-11-25 |
| 13 | 201937047926-FORM 3 [06-06-2020(online)].pdf | 2020-06-06 |