Abstract: Provided are: a pancreatic cancer detection kit and device including a nucleic acid that can specifically bind to miRNA in a specimen from a subject; and a pancreatic cancer detection method that includes the measurement of said miRNA in vitro.
Specification
Title: Pancreatic cancer detection kit or device and detection method
Technical field
[0001]
The present invention relates to a kit or device for detection of pancreatic cancer comprising nucleic acid capable of specifically binding to a specific miRNA used for examination of the presence or absence of pancreatic cancer in a subject, And measuring the expression level of the miRNA using the miRNA.
BACKGROUND ART
[0002]
The pancreas is an exocrine gland that secretes the pancreatic juice which is a digestive juice and sends it to the gastrointestinal tract via the pancreatic duct and also functions as an endocrine gland secreting hormones such as insulin and glucagon into the blood.
[0003]
As the pancreas is surrounded by many organs such as stomach and duodenum, small intestine, liver, gall bladder, it is difficult to detect cancer at an early stage, it is not accompanied by subjective symptoms, progress is very fast, metastasis to other organs It has a characteristic such as causing cancer, and it is a cancer with a very poor prognosis as compared with other cancers. According to statistics on the cancer mortality rate by site in Japan within 2011 disclosed by the National Cancer Center Research Center for Cancer Countermeasures (Tokyo, Japan), the number of deaths of pancreatic cancer is 28, As for 829 people, the five-year relative survival rate by site in 2003-2005 is the lowest in pancreatic cancer, 7.1% in males and 6.9% in females.
[0004]
As described in Non-Patent Document 1, the basics of pancreatic cancer treatment is performed by surgery, systemic chemotherapy, radiation therapy or a combination thereof according to the degree of progress. Surgery is being performed because patients with pancreatic cancer of 15 to 20% can be curable, but the majority of patients who did not undergo surgery are thought to have progressed locally or metastasized. The median survival time is said to be 8 to 12 months for locally advanced cancer and 3 to 6 months for metastatic cancer and it is very bad compared with other cancers.
[0005]
The degree of progression of pancreatic cancer by UICC (Unio Internationalis Contra Cancrum) is prescribed in the 5th edition of pancreatic cancer handling regulation (edited by the Japanese Pancreatic Society, Kanbara Publishing Co., Ltd., 2013, p. 55), and the main tumor local progression degree, lymph It is classified as stage 0, IA, IB, IIA, IIB, III, IVa, IVb by node transposition, distant metastasis, Stage I - III accounts for more than half of 5 - year survivors, and progress degree at diagnosis occupies 70% or more in Stage IVa and Stage IVb. In addition, symptoms vary depending on the site of pancreatic cancer occurrence, and in the case of pancreatic head cancer, it often develops with jaundice but there is almost no symptom in pancreatic tail cancer. Therefore, diagnosis of pancreatic tail cancer tends to be delayed compared to pancreatic head cancer.
[0006]
As described in Non-patent Document 2, abdominal ultrasonography is very useful for outpatient diagnosis and examination as a simple and minimally invasive examination in the diagnosis of pancreatic cancer. However, pancreatic cancer and small pancreatic lesions with small tumor diameter are often difficult to visualize. Abdominal ultrasonography examination in normal health examination shows a pancreatic image with an observed rate of about 1%, and pancreatic cancer detection rate is as low as about 0.06% or less. Tumor markers for pancreatic cancer detection include, for example, antigens other than sugar chains such as CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72 and urinary fucose , CEA, POA, TPS, etc. are known. As a way of using these tumor markers, cancer is suspected if its blood level is higher or lower than a previously established reference value. For example, as described in Non-Patent Document 3, the reference value of CEA is set to 5 ng / mL and the reference value of CA 19-9 is set to 37 U / mL. When the value is more than that, the pancreas Cancer including cancer is suspected. However, many tumor markers are evaluated in advanced pancreatic cancer, and in many cases early stage pancreatic cancer shows no abnormal value. In addition, even when performing tumor markers and abdominal ultrasonography at the examination, the detection rate of pancreatic cancer is low, and these screening for pancreatic cancer detection are problematic in terms of cost effectiveness.
[0007]
Although it is at the research stage, as shown in patent documents 1 to 4, the expression level of microRNA (miRNA) in a biological sample such as blood, or the expression level of miRNA and the expression level of other protein marker There is a report that discriminating pancreatic cancer by combining.
[0008]
Patent Document 1 shows a method of detecting pancreatic cancer by combining hsa-miR-125a-3p in blood with several dozen other miRNAs.
[0009]
Patent Document 2 discloses a method for producing hsa-miR-423-5p precursor, precursor of hsa-miR-423-5p, or precursor of hsa-miR-328-5p in blood or tissue, To detect pancreatic cancer in combination with miRNA.
[0010]
Patent Document 3 discloses a method of detecting pancreatic cancer by combining hsa-miR-575, hsa-miR-16-5p, or hsa-miR-24-3p in blood with other hundreds of miRNA It is shown.
[0011]
Patent Document 4 shows a method of detecting pancreatic cancer by combining hsa-miR-451a in blood and tissues with several dozen other miRNAs.
[0012]
Patent Document 5 discloses a method of detecting pancreatic cancer by combining precursor of hsa-miR-150-3p or precursor of hsa-miR-187-5p in blood or tissue with other several hundreds of miRNA Are shown.
[0013]
Non-Patent Literature 4 discloses that hsa-miR-423-5p, hsa-miR-1246, hsa-miR- 150-3p, hsa-miR-550a-5p, hsa- miR-371a-5p, hsa- Expression level in pancreatic cancer patients and healthy subjects, such as miR-1469, hsa-miR-575, hsa-miR-564, hsa-miR-125a-3p, hsa-miR- 451a, hsa- As miRNAs with significant differences.
[0014]
In non-patent document 5, plasma miR-3188, miR-16-5 p and the like are shown as miRNAs with significant difference in expression level between pancreatic cancer patients and healthy subjects.
[0015]
Non-Patent Document 6 discloses that miR-550a-5p, miR-1290, miR-24-3p, miR-486-3p, miR-423-5p, miR-125a- And miRNAs with significant differences in expression levels in healthy subjects.
[0016]
In non-patent document 7, miR-602 in the tissue is shown as a miRNA having significant difference in expression level between pancreatic cancer patient and healthy subject.
Prior Art Document
Patent literature
[0017]
Patent Document 1: Published Japanese Translation No. 2012-507300
Patent Document 2: US Patent Application Publication No. 2010/0286232
Patent Document 3: International Publication No. 2013/107459
Patent Document 4: US Patent Application Publication No. 2013/0310276 Specification
Patent Document 5: US Patent Application Publication No. 2008/0306018
Non-patent literature
[0018]
Non-Patent Document 1: Tetsuya Mine, "Pancreas", Japanese Pancreatic Society, 2007, Vol. 22, p 105-113
Non-Patent Document 2: Japan Society of Pancreatic Syndrome "Guidelines for Pancreatic Cancer Clinical Practice Based on Scientific Basis 2009" CQ 1 Diagnostic Method http: // www. suizou. org / PCMG2009 / cq1 / cq1-3. html
Non-patent document 3: Kiyomori Kurokawa ed., clinical laboratory data book, 2013, p. 633, 636 (Medical School, Tokyo, Japan)
Non-Patent Document 4: Ali S. Et al., 2010, American Journal of Translational Research, Vol. 3, (1) p
. 28-47 Non-Patent Document 5: Ganepola GA. Et al., 2014, World Journal of Gastrointestinal Oncology. Vol. 6, (1) p 22 - 33
Non-Patent Document 6: Li A. Et al., 2013, Clinical Cancer Ressearch, Vol. 19, (13), p 3600-3610
Non-Patent Document 7: Zhang J. Et al., 2014, Oncology Reports, Vol. 31, (3), p 1157 - 1164
Summary of the invention
Problem to be Solved by Invention
[0019]
An object of the present invention is to find a novel marker for pancreatic cancer tumor and to provide a method capable of effectively detecting pancreatic cancer using a nucleic acid capable of specifically binding to the marker. As described in Non-Patent Document 2, as a tumor marker for pancreatic cancer detection, for example, CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72, urine Fucose, etc., or CEA, POA, TPS, etc. as antigens other than sugar chain are known. The pancreatic cancer detection sensitivity of these tumor markers is 70 to 80% for CA 19-9, 70 to 80% for Span-1, 50 to 60% for Dupan-2, 30 to 60% for CEA, 60% for CA 50 Also, the specificity is not so high and the false positives are as high as 20 to 30%, so it is possible to erroneously detect benign tumors and / or benign diseases of other cancers and / or pancreas and / or pancreas organs Gender is also conceivable. In addition, detection sensitivity of pancreatic cancer is generally low early, and in pancreatic cancer of 2 cm or less, the positive rate of CA 19 - 9 is only half of 52%, which is useful for early detection of pancreatic cancer is not. In addition, tumor markers derived from carbohydrate antigens are inappropriate for some subjects because Lewis blood type negative cases show no false negatives because antigens are not produced.
[0020]
Although it is in the research stage, reports that discriminate pancreatic cancer using microRNA (miRNA) expression level in a biological sample such as blood are as follows, none of which has been put to practical use.
[0021]
Patent Document 1 describes a method of diagnosing various cancers including pancreatic cancer by combining hsa-miR-125a-3p in blood with dozens of other miRNAs in the blood, however, There is no description about detection performance such as specific accuracy, sensitivity, specificity, etc., and no specific method for diagnosing pancreatic cancer using blood is described.
[0022]
In Patent Document 2, the precursor of hsa-miR-204-3p in blood or tissue, the precursor of hsa-miR-423-5p, or the precursor of hsa-miR-328-5p with another several hundred A method for detecting pancreatic cancer in combination with miRNA is described, but there is no description about the detection performance such as specific accuracy, sensitivity, specificity, etc., and specific diagnosis of pancreatic cancer using blood Methods are also not described.
[0023]
In the method described in Patent Document 3, diagnosis of pancreatic cancer is performed by combining hsa-miR-575, hsa-miR-16-5p, or hsa-miR-24-3p with several hundreds of other miRNA There is no statement that it can be diagnosed with several miRNA combinations.
[0024]
In Patent Document 4, hsa-miR-451a in pancreatic cancer tissue is used for diagnosis of pancreatic cancer by combining several dozen or more other miRNAs, but concrete pancreatic cancer using blood The method of diagnosing is not described.
[0025]
In Patent Document 5, the precursor of the precursor or hsa-miR-187-5p of hsa-miR-150-3p pancreatic cancer tissues in combination with other several hundred or more miRNA in the diagnosis of pancreatic cancer However, there is no description about the detection performance such as specific accuracy, sensitivity, specificity, etc., and no specific method for diagnosing pancreatic cancer using blood is described.
[0026]
In non-patent document 4, miR-423-5p, miR-1246, miR-150-3p, miR-550a-5p, miR- Although muR-371a-5p, miR-1469, miR-575, miR-564, miR-125a-3p, miR-451a, miR- 1908-5p and the like are mentioned, their specific accuracy, sensitivity, There is no description about detection performance such as degree.
[0027]
In non-patent document 5, miR-3188, miR-16-5p and the like are listed as miRNAs whose expression level is significantly different in pancreatic cancer patients and healthy body plasmas, but as a result of the verification, reliability Is low, it is excluded from analysis targets.
[0028]
In non-patent document 6, miR-550a-5p, miR-1290, miR-24-3p, miR-486-3p, miR -423-5p, miR-125a-3p and the like are mentioned, but specific examples of miR-550a-5p, miR-24-3p, miR-486-3p, miR-423-5p, and miR-125a- There is no description about detection performance such as accuracy, sensitivity, specificity, etc., and the detection performance of miR - 1290 has not been verified with an independent specimen group.
[0029]
In Non-Patent Document 7, miR-602 and the like are listed as miRNAs having significantly different expression levels in pancreatic tissues of pancreatic cancer patients and healthy subjects, but their specific accuracy, sensitivity, specificity, etc. There is no description about detection performance and no specific method for diagnosing pancreatic cancer using blood has been described.
[0030]
As described above, in the detection of pancreatic cancer, existing tumor markers have low performance and markers at the research stage are not specifically shown for performance or detection method, so when using these There is the possibility of losing treatment opportunities by conducting useless additional examination by erroneously detecting a healthy body as a pancreatic cancer patient or overlooking a pancreatic cancer patient. In addition, measuring miRNA consisting of several tens to several hundreds increases the examination cost, so it is hard to use for large-scale screening such as medical examination. In addition, collecting pancreatic tissue to measure tumor markers is highly invasive to patients, which is undesirable, so it can be detected from blood that can be collected in a minimally invasive manner, and pancreatic cancer patients can be compared with pancreatic cancer patients , A highly accurate pancreatic cancer marker capable of correctly distinguishing a healthy body from a healthy body is required. Particularly, since pancreatic cancer is the only radical treatment for resection by early detection, a highly sensitive pancreatic cancer marker is desired.
Means for solving the problem
[0031]
As a result of intensive studies to solve the above-mentioned problems, the present inventors have found several genes that can be used as detection markers for pancreatic cancer from blood that can be collected in a minimally invasive manner, and can detect a nucleic acid capable of specifically binding thereto We found that pancreatic cancer can be detected significantly, and have completed the present invention.
[0032]
That is, the present invention has the following features.
[0033]
(1) miR-6893-5p, miR-6075, miR-6820-5p, miR-4294, miR-6729-5p, miR-4476, miR-6836-3p, miR- 6765- MiR-4634, miR-4450, miR-4792, miR-665, miR-4593, miR-6405, miR- miR-7975, miR-7109-5p, miR-6789-5p, miR-4497, miR-6877-5p, miR- 6880-5p, miR-7977, miR- 4734, miR- 6821-5p, miR- 8089, miR-5585-3p, miR-6085, mi MiR-6405-5p, miR-4651, miR-4433-3p, miR-1231, miR- 4665-5p, miR-7114-5p, miR-1238-5p, miR-8069, miR- 4732-5p, miR- 619 MiR-6505-5p, miR-6132, miR-6872-3p, miR-6875-5p , MiR-1908-3p, miR-4433b-3p, miR-4736, miR-5100, miR-6724-5p, miR-7107-5p, miR-6726-5p, miR- 3185, miR- 4638-5p, miR -1273 g - 3 p, miR - 6778 - 5 p miR-328-5p, miR-3679-3p, miR-1228-3p, miR-6779-5p, miR-4723-5p, miR-6850-5p, miR-760, miR- 7704, miR- 8072, miR- MiR-6406, miR-1913, miR-4656, miR-1260b, miR- 7106-5p, miR-6889-5p, miR-6780b- 5p, miR- 6090, miR- 4534, miR- MiR-4158, miR-3162-5p, miR-3153p, miR-5153p, miR- 1202, miR- 4467, miR- 6515-3p, miR- 4281, miR- 4505, miR- 4484, miR- 6805-3p, miR- MiR-6768-5p, miR-6721-5p, miR-1227-5p, miR-6722-3p, miR-4286, miR- 4746-3p, miR-6727-5p, miR- 6816-5p, miR- 4741, MiR-4508, miR-940, miR-4327, miR-4665-3p, miR- 718, miR- 1203, miR- 663b, miR-4258, miR- 4649-5p, miR- 4516, miR- 3619-3p, MiR-6826-5p, miR-6 At least one polynucleotide selected from the group consisting of 57-5p, miR-3131, miR-1343-3p, miR-6775-5p, miR-6813-5p, and miR- A kit for detection of pancreatic cancer, comprising a nucleic acid capable of binding to a cancer cell.
[0034]
(2) miR-6893-5p is hsa-miR-6893-5p, miR-6075 is hsa-miR-6075, miR-6820-5p is hsa-miR-6820-5p, miR-4294 Is hsa - miR - 4294, miR - 6729 - 5 p is hsa - miR - 6729 - 5 p, miR - 4476 is hsa - miR - 4476, miR - 6836 - 3 p is hsa - miR - 6836 - 3 p MiR-6765-3p is hsa-miR-6765-3p, miR-6799-5p is hsa-miR-6799-5p, miR-4530 is hsa-miR-4530, miR-7641 Is hsa-miR-7641, miR-4454 is hsa-miR-44 4, miR-615-5p is hsa-miR-615-5p, miR-8073 is hsa-miR-8073, miR-663a is hsa-miR-663a, miR-4634 is hsa- MiR-4645 is hsa-miR-4450, miR-4792 is hsa-miR-4792, miR-665 is hsa-miR-665, miR-7975 is hsa-miR- 7975, miR-7109-5p is hsa-miR-7109-5p, miR-6789-5p is hsa-miR-6789-5p, miR-4497 is hsa-miR-4497, miR- 6877-5p is hsa-miR-6877-5p, miR-688 -5p is hsa-miR-6880-5p, miR-7977 is hsa-miR-7977, miR-4734 is hsa-miR-4734, miR-6821-5p is hsa-miR-6821-5p , MiR - 8089 is hsa - miR - 8089, miR - 5585 - 3 p is hsa - miR - 5585 - 3 p, miR - 6085 is hsa - miR - 6085, miR - 6845 -5p is hsa-miR-6845-5p, miR-4651 is hsa-miR-4651, miR-4433-3p is hsa-miR-4433-3p, miR-1231 is hsa-miR-1231 , MiR-4665-5p is hsa-miR-4665-5p, miR-7114-5p is hsa-miR-7114-5p, miR-1238-5p is hsa-miR-1238-5p , MiR-8069 is hsa-miR-8069, miR-4732-5p is hsa-miR-4732-5p, miR-619-5p is hsa-miR-619-5p, miR-3622a-5p Is hsa-miR-3622a-5p, miR-1260a is hsa-miR- 260a, miR-6741-5p is hsa-miR-6741-5p, miR-6781-5p is hsa-miR-6781-5p, miR-6125 is hsa-miR-6125, miR- 6805-5p is hsa-miR-6805-5p, miR-6132 is hsa-miR-6132, miR-6872-3p is hsa-miR-6872-3p, miR-6875-5p is hsa- miR - 6875 - 5 p, miR - 1908 - 3 p is hsa - miR - 1908 - 3 p, miR - 4433 b - 3 p is hsa - miR - 4433 b - 3 p, miR - 4736 is hsa - miR - 4736 Yes, miR - 5100 is hsa - miR - 5100, miR - 6 24-5p is hsa-miR-6724-5p, miR-7107-5p is hsa-miR-7107-5p, miR-6726-5p is hsa-miR-6726-5p, miR-3185 is hsa - miR - 3185, miR - 4638 - 5 p is hsa - miR - 4638 - 5 p, miR - 1273 g - 3 p is hsa - miR - 1273 g - 3 p, miR - 6778 - 5 p is hsa - m IR-6778-5p, miR-328-5p is hsa-miR-328-5p, miR-3679-3p is hsa-miR-3679-3p, miR-1228-3p is hsa-miR- MiR-6779-5p is hsa-miR-6779-5p, miR-4723-5p is hsa-miR-4723-5p, miR-6850-5p is hsa-miR-6850- MiR - 7604 is hsa - miR - 7704, miR - 7704 is hsa - miR - 7704, miR - 8072 is hsa - miR - 8072, miR - 4486 is hsa - miR - 4486 Yes, miR-1913 is hsa-miR-1913, miR-4656 is hsa It is miR-4656, miR-1260b is hsa-miR-1260b, miR-7106-5p is hsa-miR-7106-5p, miR-6889-5p is hsa-miR-6889-5p, miR - 6780 b - 5 p is hsa - miR - 6780 b - 5 p, miR - 6090 is hsa - miR - 6090, miR - 4534 is hsa - miR - 4534, miR - 4449 is hsa - miR - 4449 MiR-5195-3p is hsa-miR-5195-3p, miR-1202 is hsa-miR-1202, miR-4467 is hsa-miR-4467, miR-6515-3p is hsa- MiR-6515-3p, miR-4281 is hs - miR - 4281, miR - 4505 is hsa - miR - 4505, miR - 4484 is hsa - miR - 4484, miR - 6805 - 3 p is hsa - miR - 6805 - 3 p, miR - 3135 b Is hsa-miR-3135b, miR-3162-5p is hsa-miR-3162-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6721-5 Pi is hsa-miR-6721-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4286 is hsa- miR-6866-5p is miR-4286, miR-4746-3p is hsa-miR-4746-3p, miR-6727-5p is hsa-miR-6727-5p, miR- 6816-5p is hsa- MiR-4508 is hsa-miR-4508, miR-940 is hsa-miR-940, miR-4327 is hsa-miR-4327 Yes, miR-4665-3p is hsa-miR-4665-3p, miR MiR-4258 is hsa-miR-4258, miR-4649-m is a hsa-miR-663b, miR- Mp-miR-4649-5p, miR-4516 is hsa-miR-4516, miR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR- 6826-5p, miR-6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p, MiR-6775-5p is hsa-miR-6775-5p, mi -6813-5p is hsa-miR-6813-5p, and, miR-3940-5p is hsa-miR-3940-5p, kit according to (1). 3p is hsa-miR-4746-3p, miR-6727-5p is hsa-miR-6727-5p, miR-6816-5p is hsa-miR-6816-5p, miR-4741 is hsa- a miR-4741, miR-4508 is hsa-miR-4508, miR-940 is hsa-miR-940, miR-4327 is hsa-miR-4327, the miR-4665-3p hsa- is a miR-4665-3p, miR-718 is hsa-miR-718, miR-1203 is hsa-miR-1203, miR-663b is hsa-miR-663b, miR-4258 is hsa- miR-4258, miR-4649-5p is hsa-miR-46 9-5p, miR-4516 is hsa-miR-4516, miR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR-6826-5p, miR-6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p, miR-6775-5p is (1), wherein miR-hsa-miR-6775-5p, miR-6813-5p is hsa-miR-6813-5p, and miR-3940-5p is hsa-miR-3940-5p kit. 3p is hsa-miR-4746-3p, miR-6727-5p is hsa-miR-6727-5p, miR-6816-5p is hsa-miR-6816-5p, miR-4741 is hsa- a miR-4741, miR-4508 is hsa-miR-4508, miR-940 is hsa-miR-940, miR-4327 is hsa-miR-4327, the miR-4665-3p hsa- is a miR-4665-3p, miR-718 is hsa-miR-718, miR-1203 is hsa-miR-1203, miR-663b is hsa-miR-663b, miR-4258 is hsa- miR-4258, miR-4649-5p is hsa-miR-46 9-5p, miR-4516 is hsa-miR-4516, miR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR-6826-5p, miR-6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p, miR-6775-5p is (1), wherein miR-hsa-miR-6775-5p, miR-6813-5p is hsa-miR-6813-5p, and miR-3940-5p is hsa-miR-3940-5p kit. Ri, miR-1203 is hsa-miR-1203, miR-663b is hsa-miR-663b, miR-4258 is hsa-miR-4258, miR-4649-5p is hsa-miR-4649- MiR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR-6826-5p, miR- 6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p, miR-6775-5p is hsa- miR-6775-5p, miR-6813-5p is hsa-miR- A 813-5P, and, miR-3940-5p is hsa-miR-3940-5p, kit according to (1). Ri, miR-1203 is hsa-miR-1203, miR-663b is hsa-miR-663b, miR-4258 is hsa-miR-4258, miR-4649-5p is hsa-miR-4649- MiR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR-6826-5p, miR- 6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p, miR-6775-5p is hsa- miR-6775-5p, miR-6813-5p is hsa-miR- A 813-5P, and, miR-3940-5p is hsa-miR-3940-5p, kit according to (1).
[0035]
(3) The polynucleotide according to any one of the following (a) to (e):
(a) a nucleotide sequence represented by any one of SEQ ID NOS : 1 to 104, 464 to 473, and 492 to 494 Or a polynucleotide consisting of a nucleotide sequence in which u is t in the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases,
(b) SEQ ID NOs: 1 to 104, 464 to 473, and A polynucleotide comprising a nucleotide sequence represented by any one of 492 to 494,
(c) a nucleotide sequence represented by any one of SEQ ID NOS: 1 to 104, 464 to 473, and 492 to 494, or t, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases,
(d) a polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: A polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the nucleotide sequence, and
(e)
(1) or (2), wherein the polynucleotide is a polynucleotide selected from the group consisting of a polynucleotide that hybridizes with the polynucleotide of any one of (a) to (d) under stringent conditions .
[0036]
(4) The method according to (1), wherein miR-125a-3p, miR-204-3p, miR- 1469, miR-575, miR- 150-3p, miR-423-5p, miR-564, miR- 3188, miR- , MiR - 602, miR - 1290, miR - 16 - 5 p, miR - 451 a, miR - 24 - 3 p, miR - 187 - 5 p, miR - 1908 - 5 p, miR - 371 a - 5 p and miR - 550 a - 5 p The kit according to any one of (1) to (3), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group.
[0037]
(5) miR-125a-3p is hsa-miR-125a-3p, miR-204-3p is hsa-miR-204-3p, miR-1469 is hsa-miR-1469, miR-575 Is hsa - miR - 575, miR - 150 - 3 p is hsa - miR - 150 - 3 p, miR - 423 - 5 p is hsa - miR - 423 - 5 p and miR - 564 is hsa - miR - 564 , MiR - 3188 is hsa - miR - 3188, miR - 1246 is hsa - miR - 1246, miR - 602 is hsa - miR - 602, miR - 1290 is hsa - miR - 1290 , MiR-16-5p is hsa-miR-16-5p, miR-451a is hsa-miR 451a, miR-24-3p is hsa-miR-24-3p, miR-187-5p is hsa-miR-187-5p, miR-1908-5p is hsa-miR-1908-5p A kit according to (4), wherein miR-371a-5p is hsa-miR-371a-5p and miR-550a-5p is hsa-miR-550a-5p.
[0038]
(6) The polynucleotide according to any one of (f) to (j) below:
(f) a nucleotide sequence represented by any one of SEQ ID NOs : 105 to 122 or a nucleotide sequence in which u is t a polynucleotide consisting of a certain nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 105-122,
( h) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, A fragment thereof containing consecutive bases,
(i) a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122, or a base sequence in which u is t in the nucleotide sequence Polynucleotide comprising a nucleotide sequence complementary to sequence, and
(j) wherein (f) any of the polynucleotides under stringent conditions with a polynucleotide hybridizing of ~ (i),
poly selected from the group consisting of The kit according to (4) or (5), further comprising a nucleotide.
[0039]
(7) The method according to (7), wherein miR-4417, miR-4707-5p, miR-7847-3p, miR-2861, miR- 4513, miR-7111-5p, miR-6777-5p, miR-7113-3p, miR MiR-3184-5p, miR-4271, miR-6791-5p, miR-642a-3p, miR-7108-5p, miR-128-1-5p, miR-5196-5p, miR- 3178, miR -3656, miR - 92a - 2 - 5 p, miR - 6769 b - 5 p, miR - 4689, miR - 6076, miR - 92 b - 5 p, miR - 6774 - 5 p, miR - 486 - 3 p, miR - 6806 - 5 p, miR -6842-5p, miR-6716-5p, miR-557, miR-46 3, miR - 4674, miR - 4442, miR - 1915 - 3 p, miR - 4687 - 3 p and miR - 92 b - 3 p with a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of The kit according to any one of (1) to (6), further including:
[0040]
(8) miR-4417 is hsa-miR-4417, miR-4707-5p is hsa-miR-4707-5p, miR-7847-3p is hsa-miR-7847-3p, miR-2861 Is hsa - miR - 2861, miR - 4513 is hsa - miR - 4513, miR - 7111 - 5 p is hsa - miR - 7111 - 5 p, miR - 6777 - 5 p is hsa - miR - 6777 - 5 p , MiR-7113-3p is hsa-miR-7113-3p, miR-4648 is hsa-miR-4648, miR-3184-5p is hsa-miR-3184-5p, miR-4271 Is hsa-miR-4271, miR-6791-5p is hsa-miR 6791-5p, miR-642a-3p is hsa-miR-642a-3p, miR-7108-5p is hsa-miR-7108-5p, miR-128-1-5p is hsa-miR- MiR-3196-5p is hsa-miR-5196-5p, miR-3178 is hsa-miR-3178, miR-3656 is hsa-miR-3656, miR- MiR-6769b-5p is hsa-miR-6669b-5p, miR-4689 is hsa-miR-4689, miR-6076 is hsa-miR-6076, miR-92b-5p is hsa-miR-92b-5p, iR-6774-5p is hsa-miR-6774-5p, miR-486-3p is hsa-miR-486-3p, miR-6806-5p is hsa-miR-6806-5p, miR- 6842-5p is hsa-miR-6842-5p, miR-6716-5p is hsa-miR-6716-5p, miR-557 is hsa-miR-557, miR-4673 is hsa-miR- 4
[0041]
(9) The polynucleotide according to any one of the following (k) to (o):
(k) a nucleotide sequence represented by any one of SEQ ID NOs : 349 to 383 or a nucleotide sequence in which u is t a polynucleotide consisting of a certain nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (l) SEQ ID NO: 349-383,
( m) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 349 to 383 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, a fragment containing consecutive bases,
base sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 349 to 383 Polynucleotide comprising a nucleotide sequence complementary to sequence, and
(o) the (k) any of the polynucleotides stringent polynucleotide hybridizing under conditions of ~ (n),
poly selected from the group consisting of The kit according to (7) or (8), further comprising a nucleotide.
[0042]
(10) The kit according to (1) or (2), wherein at least two or more nucleic acids capable of specifically binding to each of at least two or more polynucleotides selected from all the pancreatic cancer markers described in The kit according to any one of (1) to (9), which comprises:
[0043]
(11) miR-6893-5p, miR-6075, miR-6820-5p, miR-4294, miR-6729-5p, miR-4476, miR-6836-3p, miR-6765- MiR-4634, miR-4450, miR-4792, miR-665, miR-4593, miR-6405, miR-615-5p, miR- miR-7975, miR-7109-5p, miR-6789-5p, miR-4497, miR-6877-5p, miR- 6880-5p, miR-7977, miR- 4734, miR- 6821-5p, miR- 8089, miR-5585-3p, miR-6085, m MiR-6405-5p, miR-4651, miR-4433-3p, miR-1231, miR- 4665-5p, miR-7114-5p, miR-1238-5p, miR- 8069, miR- 4732-5p, miR- 619-5p, miR-3622a-5p, miR-1260a, miR-6741-5p, miR-6781-5p, miR-6125, miR-6805-5p, miR- 6132, miR- 6872-3p, miR- MiR-7107-5p, miR-6726-5p, miR-3185, miR-4638-5p, miR-6738-5p, miR- MiR-1273 g-3 p, miR-6778-5 , MiR-728-5p, miR-3679-3p, miR-1228-3p, miR-6779-5p, miR-4723-5p, miR-6850-5p, miR-760, miR-7704, miR- 8072, miR -4486, miR - 1913, miR - 4656, miR - 1260 b, miR - 7106 - 5 p, miR - 6889 - 5 p, miR - 6780 b - 5 p, miR - 6090, miR - 4534, miR -4449, miR-5195-3p, miR-1202, miR-4467, miR-6515-3p, miR-4281, miR-4505, miR-4484, miR-6805-3p, miR- 3135b, miR- , MiR-6768-5p, miR-6721-5p, miR-1227-5p, miR-6722-3p, miR-4286, miR- 4746-3p, miR-6727-5p, miR-6816-5p, miR- 4741 , MiR-4508, miR-940, miR-4327, miR-4665-3p, miR- 718, miR-1203, miR- 663b, miR- 4258, miR- 4649-5p, miR- 4516, miR- 3619-3p , MiR-6826-5p, miR- At least one polynucleotide selected from the group consisting of 757-5p, miR-3131, miR-1343-3p, miR-6775-5p, miR-6813-5p, and miR- A nucleic acid capable of binding to a cancer cell.
[0044]
(12) miR-6893-5p is hsa-miR-6893-5p, miR-6075 is hsa-miR-6075, miR-6820-5p is hsa-miR-6820-5p, miR-4294 Is hsa - miR - 4294, miR - 6729 - 5 p is hsa - miR - 6729 - 5 p, miR - 4476 is hsa - miR - 4476, miR - 6836 - 3 p is hsa - miR - 6836 - 3 p MiR-6765-3p is hsa-miR-6765-3p, miR-6799-5p is hsa-miR-6799-5p, miR-4530 is hsa-miR-4530, miR-7641 Is hsa-miR-7641, miR-4454 is hsa-miR-4 54, miR-615-5p is hsa-miR-615-5p, miR-8073 is hsa-miR-8073, miR-663a is hsa-miR-663a, miR-4634 is hsa- is a miR-4634, miR-4450 is hsa-miR-4450, miR-4792 is hsa-miR-4792, miR-665 is hsa-miR-665, miR-7975 is hsa-miR- 7975, miR-7109-5p is hsa-miR-7109-5p, miR-6789-5p is hsa-miR-6789-5p, miR-4497 is hsa-miR-4497, miR- 6877-5p is hsa-miR-6877-5p, miR-68 MiR-6821-5p is hsa-miR-6880-5p, miR-7977 is hsa-miR-7977, miR-4734 is hsa-miR- 4734, miR-6821-5p is hsa- MiR-8089 is hsa-miR-8089, miR-5585-3p is hsa-miR-5585-3p, miR-6085 is hsa-miR-6085, miR-684 Mp-miR-6845-5p, miR-4651 is hsa-miR-4651, miR-4433-3p is hsa-miR-4433-3p, miR-1231 is hsa-miR- 1231-5-5p is hsa-miR-4665-5p, miR-7114-5p is hsa-miR-7114-5p, miR-1238-5p is hsa-miR-1238-5p MiR-8099 is hsa-miR-8069, miR-4732-5p is hsa-miR-4732-5p, miR-619-5p is hsa-miR-619-5p, miR-3622a- 5p is hsa-miR-3622a-5p, miR-1260a is hsa-miR 1260a, miR-6741-5p is hsa-miR-6741-5p, miR-6781-5p is hsa-miR-6781-5p, miR-6125 is hsa-miR-6125, miR- 6805-5p is hsa-miR-6805-5p, miR-6132 is hsa-miR-6132, miR-6872-3p is hsa-miR-6872-3p, miR-6875-5p is hsa- MiR - 6875 - 5 p, miR - 1908 - 3 p is hsa - miR - 1908 - 3 p, miR - 4433 b - 3 p is hsa - miR - 4433 b - 3 p, miR - 4736 is hsa - miR - 4736 Yes, miR-5100 is hsa-miR-5100, miR- 724-5p is hsa-miR-6724-5p, miR-7107-5p is hsa-miR-7107-5p, miR-6726-5p is hsa-miR-6726-5p, miR-3185 is hsa - miR - 3185, miR - 4638 - 5 p is hsa - miR - 4638 - 5 p, miR - 1273 g - 3 p is hsa - miR - 1273 g - 3 p, miR - 6778 - 5 p is hsa - miR-6778-5p, miR-328-5p is hsa-miR-328-5p, miR-3679-3p is hsa-miR-3679-3p, miR-1228-3p is hsa-miR- MiR-6779-5p is hsa-miR-6779-5p, miR-4723-5p is hsa-miR-4723-5p, miR-6850-5p is hsa-miR-6850- is 5p, miR-760 is hsa-miR-760, miR-7704 is hsa-miR-7704, miR-8072 is hsa-miR-8072, miR-4486 is in hsa-miR-4486 Yes, miR-1913 is hsa-miR-1913, miR-4656 is hs - miR - 4656, miR - 1260 b is hsa - miR - 1260 b, miR - 7106 - 5 p is hsa - miR - 7106 - 5 p, miR - 6889 - 5 p is hsa - miR - 6889 - 5 p , miR-6780b-5p is hsa-miR-6780b-5p, miR-6090 is hsa-miR-6090, miR-4534 is hsa-miR-4534, miR-4449 is hsa-miR-4449 , MiR-5195-3p is hsa-miR-5195-3p, miR-1202 is hsa-miR-1202, miR-4467 is hsa-miR-4467, miR-6515-3p is hsa -miR-6515-3p, miR-4281 is h Is a a-miR-4281, miR-4505 is hsa-miR-4505, miR-4484 is hsa-miR-4484, miR-6805-3p is hsa-miR-6805-3p, miR- 3135b is hsa-miR-3135b, miR-3162-5p is hsa-miR-3162-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6721- 5p is hsa-miR-6721-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4286 is hsa- MiR-6866-5p is miR-4286, miR-4746-3p is hsa-miR-4746-3p, miR-6727-5p is hsa- miR-6727-5p, miR- 6816-5p is hsa- a 5p, miR-4741 is hsa-miR-4741, miR-4508 is hsa-miR-4508, miR-940 is hsa-miR-940, miR-4327 is in the hsa-miR-4327 Yes, miR-4665-3p is hsa-miR-4665-3p, mi -718 is hsa-miR-718, miR-1203 is hsa-miR-1203, miR-663b is hsa-miR-663b, miR-4258 is hsa-miR-4258, miR-4649 -51p is hsa-miR-4649-5p, miR-4516 is hsa-miR-4516, miR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR -6826-5p, miR-6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p , MiR-6775-5p is hsa-miR-6775-5p, m R-6813-5p is hsa-miR-6813-5p, and, miR-3940-5p is hsa-miR-3940-5p, according to (11) device.
[0045]
(13) The polynucleotide according to any one of the following (a) to (e):
(a) a nucleotide sequence represented by any one of SEQ ID NOS : 1 to 104, 464 to 473, and 492 to 494 Or a polynucleotide consisting of a nucleotide sequence in which u is t in the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases,
(b) SEQ ID NOs: 1 to 104, 464 to 473, and A polynucleotide comprising a nucleotide sequence represented by any one of 492 to 494,
(c) a nucleotide sequence represented by any one of SEQ ID NOS: 1 to 104, 464 to 473, and 492 to 494, or t, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases,
(d ) a polynucleotide consisting of a base sequence complementary to the base sequence ) A polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the nucleotide sequence, and
(e
The device according to (11) or (12), wherein the polynucleotide is a polynucleotide selected from the group consisting of a polynucleotide that hybridizes with the polynucleotide of any one of (a) to (d) under stringent conditions .
[0046]
(14) The method according to (14), wherein the device is a miR-125a-3p, miR-204-3p, miR- 1469, miR-575, miR- 150-3p, miR- 423-5p, miR- MiR-187-5p, miR-1908-5p, miR-371a-m, and miR-368, miR- 1246, miR- 602, miR- 1290, miR- 16-5 p, miR- 451a, miR- (11) to (13), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of 5p and miR-550a-5p.
[0047]
(15) miR-125a-3p is hsa-miR-125a-3p, miR-204-3p is hsa-miR-204-3p, miR-1469 is hsa- miR-1469, miR-575 Is hsa - miR - 575, miR - 150 - 3 p is hsa - miR - 150 - 3 p, miR - 423 - 5 p is hsa - miR - 423 - 5 p and miR - 564 is hsa - miR - 564 , MiR - 3188 is hsa - miR - 3188, miR - 1246 is hsa - miR - 1246, miR - 602 is hsa - miR - 602, miR - 1290 is hsa - miR - 1290 , MiR-16-5p is hsa-miR-16-5p, miR-451a is hsa-mi -451a, miR-24-3p is hsa-miR-24-3p, miR-187-5p is hsa-miR-187-5p, miR-1908-5p is hsa-miR-1908-5p (14), wherein miR-371a-5p is hsa-miR-371a-5p and miR-550a-5p is hsa-miR-550a-5p.
[0048]
(16) The polynucleotide according to any one of (f) to (j) below:
(f) a nucleotide sequence represented by any one of SEQ ID NOs : 105 to 122, or a nucleotide sequence in which u is t a polynucleotide consisting of a certain nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 105-122,
( h) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, A fragment thereof containing consecutive bases,
(i) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or a base in which u is t in the base sequence Polynucleotide comprising a nucleotide sequence complementary to the sequence, and
any polynucleotide and a polynucleotide hybridizing under stringent conditions, the (j) wherein (f) ~ (i)
poly selected from the consisting of group The device according to (14) or (15), which is a nucleotide.
[0049]
(17) The method according to any one of (1) to (17), wherein the device is another pancreatic cancer marker, miR-4417, miR-4707-5p, miR-7847-3p, miR-2861, miR- 4513, miR- 7111-5p, miR- MiR-7113-3p, miR-7113-3p, miR-4648, miR-3184-5p, miR-4271, miR- 6791-5p, miR-642a-3p, miR- 7108-5p, miR- 128-1-5p, miR- 5196-5p, miR-3178, miR-3656, miR-92a-2-5p, miR-6769b-5p, miR- 4689, miR- 6076, miR-92b- 5p, miR- 6774-5p, miR- 3p, miR-6806-5p, miR-6842-5p, miR-6716- at least one polynucleotide selected from the group consisting of p, miR-557, miR-4673, miR-4674, miR-4442, miR- 1915-3p, miR-4687-3p and miR-92b- The device according to any one of (11) to (16), further comprising a nucleic acid capable of specifically binding.
[0050]
(18) miR-4417 is hsa-miR-4417, miR-4707-5p is hsa-miR-4707-5p, miR-7847-3p is hsa-miR-7847-3p, miR-2861 Is hsa - miR - 2861, miR - 4513 is hsa - miR - 4513, miR - 7111 - 5 p is hsa - miR - 7111 - 5 p, miR - 6777 - 5 p is hsa - miR - 6777 - 5 p , MiR-7113-3p is hsa-miR-7113-3p, miR-4648 is hsa-miR-4648, miR-3184-5p is hsa-miR-3184-5p, miR-4271 Is hsa - miR - 4271, miR - 6791 - 5 p is hsa - mi -6791-5 p, miR-642a-3p is hsa-miR-642a-3p, miR-7108-5p is hsa-miR-7108-5p, miR-128-1-5p is hsa-miR -128-1-5p, miR-5196-5p is hsa-miR-5196-5p, miR-3178 is hsa-miR-3178, miR-3656 is hsa-miR-3656, miR -92a-2-5p is hsa-miR-92a-2-5p, miR-6769b-5p is hsa-miR-6769b-5p, miR-4689 is hsa-miR-4689, miR-6076 Is hsa-miR-6076, miR-92b-5p is hsa-miR-92b-5p miR-6774-5p is hsa-miR-6774-5p, miR-486-3p is hsa-miR-486-3p, miR-6806-5p is hsa-miR-6806-5p, miR- 6842-5p is hsa-miR-6842-5p, miR-6716-5p is hsa-miR-6716-5p, miR-557 is hsa-miR-557, miR-4673 is hsa-miR-
[0051]
(19) The polynucleotide according to any one of (k) to (o) below:
(k) a nucleotide sequence represented by any one of SEQ ID NOs : 349 to 383 or a nucleotide sequence in which u is t a polynucleotide consisting of a certain nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (l) SEQ ID NO: 349-383,
( m) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 349 to 383 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a polynucleotide comprising 15 or more a fragment containing consecutive bases,
and u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 349 to 383 bases Polynucleotide comprising a nucleotide sequence complementary to the sequence, and
(o) the (k) any of the polynucleotides under stringent conditions with a polynucleotide hybridizing of ~ (n),
poly selected from the group consisting of The device according to (17) or (18), which is a nucleotide.
[0052]
(20) The device according to any one of (11) to (19), wherein the device is a device for measurement by a hybridization technique.
[0053]
(21) The device according to (20), wherein the hybridization technique is nucleic acid array technology.
[0054]
(22) The method according to (22), wherein the device comprises at least two or more nucleic acids capable of specifically binding to each of at least two or more polynucleotides selected from all pancreatic cancer markers according to (11) or (12) The device according to any one of (11) to (21), which comprises:
[0055]
(23) A kit according to any one of (1) to (10) or the device according to any one of (11) to (22) is used to measure the expression level of a target nucleic acid in a specimen of a subject, Using the measured expression level and the control expression level of a healthy body measured in the same manner, it is confirmed that the subject is suffering from pancreatic cancer or that it is not suffering from pancreatic cancer in vitro And evaluating with pancreatic cancer.
[0056]
(24) The method according to (23), wherein the subject is a human.
[0057]
(25) The method according to (23) or (24), wherein the specimen is blood, serum or plasma.
[0058]
The terms used in the present specification have the following definitions.
[0059]
As used herein, "pancreatic cancer" refers to all malignant tumors formed in the pancreas. Specifically, it includes serous cystadenocarcinoma, mucinous cystadenocarcinoma, papillary ductal papillary mucinous adenocarcinoma, invasive pancreatic ductal carcinoma, acinar cell carcinoma, neuroendocrine carcinoma and the like (see "Handling of pancreatic cancer", No. 6 Version supplement edition, 2013, The Japanese Pancreatic Society, Kanbara publication, p. 21-22).
[0060]
As used herein, "benign tumor and / or benign disease of pancreas and / or peripheral organs of the pancreas" refers to diseases of non-malignant tumors related to pancreas, liver, and biliary tract.
[0061]
In addition, the abbreviated designation of "nucleotide", "polynucleotide", "DNA", "RNA" and the like as used in this specification means "guideline for preparation of specifications including nucleotide sequence or amino acid sequence" (Edited by Japan Patent Office) and usual in the technical field.
[0062]
As used herein, the term "polynucleotide" is used for nucleic acids encompassing both RNA, DNA, and RNA / DNA (chimeric). Incidentally, the DNA includes cDNA, genomic DNA, and synthetic DNA. In addition, the above RNA includes total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA and synthetic RNA. In the present specification, "synthetic DNA" and "synthetic RNA" are synthesized artificially (for example, using an automatic nucleic acid synthesizer) on the basis of a predetermined base sequence (which may be either a natural type sequence or a non- Refers to DNA and RNA prepared. As used herein, the term "non-naturally occurring sequence" is intended to be used in a broad sense and refers to a sequence that differs from the native sequence, eg, that contains substitutions, deletions, insertions and / or additions of one or more nucleotides Ie, mutant sequences), sequences comprising one or more modified nucleotides (ie, modified sequences), and the like. Also, as used herein, polynucleotides are used interchangeably with nucleic acids.
[0063]
In the present specification, the term "fragment" is a polynucleotide having a nucleotide sequence of consecutive portions of a polynucleotide, and desirably has a length of 15 bases or more, preferably 17 bases or more, and more preferably 19 bases or more .
[0064]
As used herein, the term "gene" includes not only RNA and double-stranded DNA, but also single strand DNA such as a positive strand (or sense strand) or a complementary strand (or antisense strand) constituting it To be used. And it is not particularly limited by its length.
[0065]
Therefore, in the present specification, the term "gene" means a double-stranded DNA containing human genomic DNA, a single-stranded DNA (cDNA) containing cDNA, a single strand having a sequence complementary to the normal strand DNA (complementary strand), microRNA (miRNA), and fragments thereof, and transcription products thereof. Also, the "gene" includes not only "gene" represented by a specific nucleotide sequence (or SEQ ID NO:) but also RNA having biological function equivalent to RNA encoded by them, such as homologues Or orthologs), mutants such as gene polymorphisms, and "nucleic acids" encoding derivatives. Specific examples of the "nucleic acid" encoding such a homologue, mutant or derivative include the nucleotide sequence represented by any one of SEQ ID NOS: 1 to 499, or the nucleotide sequence represented by SEQ ID NO: 1 to 499 under stringent conditions described later A nucleic acid having a nucleotide sequence that hybridizes with a complementary sequence of a nucleotide sequence in which u is t in the sequence. The term "gene" does not refer to a functional region but may include, for example, an expression control region, a coding region, an exon or an intron. In addition, the "gene" may be contained in a cell, may be released alone outside the cell, or may be in a state encapsulated in a vesicle called exosome.
[0066]
As used herein, "exosome" (aka "exosome") is a vesicle encased by a lipid bilayer membrane secreted from cells. Exosomes are derived from multispecial endosomes and may contain biological substances such as "genes" such as RNA and DNA and proteins, when released into the extracellular environment. Exosomes are known to be contained in body fluids such as blood, serum, plasma, serum, lymph fluid and the like.
[0067]
The term "transcription product" as used herein refers to RNA synthesized using the DNA sequence of a gene as a template. RNA is synthesized in such a way that RNA polymerase binds to a site called a promoter located upstream of the gene and ribonucleotides are linked to the 3 'end so that it is complementary to the DNA base sequence. This RNA includes not only the gene itself but also the whole sequence from the transcription initiation site including the expression control region, coding region, exon or intron to the end of the poly A sequence.
[0068]
In the present specification, "microRNA (miRNA)" means a protein complex which is transcribed as an RNA precursor having a hairpin-like structure and cleaved by a dsRNA cleaving enzyme having an RNase III cleaving activity, and which is called RISC , And non-coding RNA of 15 to 25 bases involved in mRNA translation suppression is intended to be used. "MiRNA" used in the present specification includes not only "miRNA" represented by a specific nucleotide sequence (or SEQ ID NO:), but also precursor (pre-miRNA, pri-miRNA) of the "miRNA" Also included are miRNAs that are equivalent in biological function, such as homologues (ie, homologs or orthologs), variants such as gene polymorphisms, and derivatives. Specifically, such precursors, homologues, mutants or derivatives can be identified by miRBase release 20 (http://www.mirbase.org/) and can be identified under stringent conditions as described later , And "miRNA" having a nucleotide sequence that hybridizes with a complementary sequence of any of the specific nucleotide sequences represented by any one of SEQ ID NOS: 1 to 499. Furthermore, "miRNA" used in the present specification may be a gene product of the miR gene, and such a gene product may be a mature miRNA (for example, a miRNA as described above, 25 bases, or 19 to 25 bases non-coding RNA) or miRNA precursor (eg, pre-miRNA or pri-miRNA as described above).
[0069]
As used herein, the term "probe" includes a polynucleotide used for specifically detecting RNA generated by expression of a gene or a polynucleotide derived therefrom and / or a polynucleotide complementary thereto.
[0070]
As used herein, the term "primer" includes a polynucleotide that specifically recognizes and amplifies RNA generated by expression of a gene or a polynucleotide derived therefrom, and / or a polynucleotide complementary thereto.
[0071]
Here, the complementary polynucleotide (complementary strand, reverse strand) refers to a polynucleotide consisting of a nucleotide sequence defined by any one of SEQ ID NOS: 1 to 499, or a nucleotide sequence in which u is t in the nucleotide sequence Based on the base pair relationship such as A: T (U), G: C with respect to the full-length sequence or partial sequence thereof (for convenience, this is referred to as a positive strand in this case), it is basically complementary Means a polynucleotide. However, such a complementary strand is not limited to a case where it forms a perfect complementary sequence to the base sequence of a target normal strand, and has a complementary relationship to such a degree that it can hybridize with a target normal strand under stringent conditions It may be.
[0072]
As used herein, the term "stringent conditions" means that nucleic acid probes are detectable to a greater extent than other sequences (eg, average of background measurements + standard error of background measurements × 2 or more measured values ), And refers to a condition under which it hybridizes to the target sequence. Stringent conditions are sequence-dependent and will vary depending on the environment in which hybridization is performed. By controlling the stringency of the hybridization and / or wash conditions, target sequences that are 100% complementary to the nucleic acid probe can be identified. Specific examples of "stringent conditions" will be described later.
[0073]
As used herein, "Tm value" means the temperature at which the double-stranded portion of the polynucleotide is denatured into a single strand and the double strand and the single strand are present in a 1: 1 ratio.
[0074]
The term "variant" as used herein refers to a naturally occurring mutant resulting from polymorphism, mutation, etc. in the case of a nucleic acid, or a nucleotide sequence of any one of SEQ ID NOS: 1 to 499, or u t, or a mutant comprising deletion, substitution, addition, or insertion of one or more bases in the partial sequence thereof, or a mutant comprising about 90% or more, about 95% or more, Or more, about 97% or more, about 98% or more, about 99% or more, or a polynucleotide or oligonucleotide containing the base sequence or its partial sequence under stringent conditions as defined above Means a nucleic acid to be soyed.
[0075]
As used herein, "several" means about 10, 9, 8, 7, 6, 5, 4, 3 or 2 integers.
[0076]
In the present specification, mutants can be prepared by well-known techniques such as site-directed mutagenesis, mutagenesis using PCR method, and the like.
[0077]
As used herein, "% identity" can be determined using the protein or gene search system with BLAST or FASTA described above, introducing gaps or without introducing gaps (Zheng Zhang et al. Altschul, S. F. et al., 1990, Journal of Molecular Biology, Vol. 215, p 403-410; Pearson, W. R. et al., 2000, J. Comput. Biol., 7, 1988, Proc. Natl. Acad. Sci. U. S. A., Vol. 85, p 2444 - 2448).
[0078]
As used herein, the term "derivative" refers to a modified nucleic acid, including but not limited to, for example, a labeled derivative such as with a fluorophore, a modified nucleotide such as alkyl, such as halogen, methyl, alkoxy such as methoxy, methoxy, Nucleotides and bases containing nucleotides and nucleotides, saturated double bonds, deamination, substitution of oxygen molecules with sulfur molecules, etc), PNA (peptide nucleic acid; Nielsen, P.E. LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, p. 5401-5404), and the like .
[0079]
In the present specification, a "nucleic acid" capable of specifically binding to a polynucleotide selected from miRNA which is a pancreatic cancer marker is a nucleic acid synthesized or prepared, specifically, a "nucleic acid probe" or In order to detect the presence or absence of pancreatic cancer in a subject or to detect the presence or absence of pancreatic cancer, the degree of morbidity, the presence or absence of improvement in pancreatic cancer and the degree of improvement, the pancreas In order to diagnose susceptibility to treatment or to screen candidate substances useful for the prevention, improvement or treatment of pancreatic cancer, directly or indirectly. They specifically recognize transcripts represented by any one of SEQ ID NOS: 1 to 499 or cDNA-synthesized nucleic acids thereof in specimens such as bodily fluids such as blood and urine, in association with the disease of pancreatic cancer Nucleotides, oligonucleotides and polynucleotides that can be ligated. These nucleotides, oligonucleotides and polynucleotides can be used as probes for detecting the above-mentioned genes expressed in vivo, tissues, intracellularly and the like based on the above properties, and also as probes for amplifying the above- It can be effectively used as a primer.
[0080]
The term "detection" as used herein may be replaced with the terms test, measurement, detection or determination assistance. Also, in the present specification, the term "evaluation" is used in the meaning including supporting diagnosis or evaluation based on examination results or measurement results.
[0081]
"Subject" as used herein includes humans, primates including chimpanzees, pet animals such as dogs, cats, livestock animals such as cattle, horses, sheep, goats, rodents such as mice, rats and the like Of mammals. "Healthy body" is also an animal that is such a mammal and does not suffer from the cancer to be detected.
[0082]
As used herein, "P" or "P value" refers to the probability that an extreme statistic will be observed in statistical tests than the statistics actually calculated from the data under the null hypothesis . Therefore, the smaller "P" or "P value" is, the more significant difference can be assumed between the comparison objects.
[0083]
In the present specification, "sensitivity" means the value of (number of true positives) / (number of true positives + number of false negatives). If the sensitivity is high, it will be possible to detect pancreatic cancer at an early stage, which will result in complete resection of the cancer and reduction of the recurrence rate.
[0084]
In the present specification, "specificity" means (number of true negatives) / (number of true negative + false positive number). If the specificity is high, it prevents useless additional examination by erroneously discriminating healthy bodies as pancreatic cancer patients, which leads to reduction of burden on patients and reduction of medical expenses.
[0085]
In the present specification, "accuracy" means a value of (the number of true positives + the number of true negatives) / (the number of all cases). The accuracy indicates the rate at which the discrimination result for all the specimens was correct, which is the first index for evaluating the detection performance.
[0086]
The "specimen" to be judged, detected or diagnosed in the present specification means that the expression of the gene of the present invention changes with the occurrence of pancreatic cancer, progression of pancreatic cancer, and exercise effect on pancreatic cancer Tissues and biomaterials. Specifically, it includes the pancreas tissues and surrounding vasculature, lymph nodes and organs, organs, skin and metabolically suspected organs, skin, and body fluids such as blood, urine, saliva, sweat, tissue leachate, serum prepared from blood, plasma , Other, feces, hair and the like. Furthermore, it refers to genes such as biological samples extracted from these, specifically RNA or miRNA.
[0087]
The term "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" as used herein refers to the hsa-miR-6893-5p gene (miRBase Accession No. 1, MIMAT0027686) and other organism homologs or orthologs and the like. The hsa-miR-6893-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6893-5p" is known as "hsa-mir-6893" (miRBase Accession No. MI0022740, SEQ ID NO: 123) which has a hairpin-like structure as its precursor.
[0088]
The term "hsa-miR-6075 gene" or "hsa-miR-6075" as used herein refers to the hsa-miR-6075 gene (miRBase Accession No. MIMAT0023700) set forth in SEQ ID NO: 2 and other species Homologs or orthologs and the like are included. The hsa-miR-6075 gene is described in Voellenkle C et al., 2012, RNA. , Vol. 18, pp. 472-484. Also, "hsa-miR-6075" is known as "hsa-mir-6075" (miRBase Accession No. MI 0020352, SEQ ID NO: 124) which has a hairpin-like structure as its precursor.
[0089]
The term "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" as used herein refers to the hsa-miR-6820-5p gene (miRBase Accession No. 1, MIMAT0027540) and other species species homologs or orthologs and the like. The hsa-miR-6820-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6820-5p" is known as "hsa-mir-6820" (miRBase Accession No. MI 00 22665, SEQ ID NO: 125) which has a hairpin-like structure as its precursor.
[0090]
The term "hsa-miR-4294 gene" or "hsa-miR-4294" as used herein refers to the hsa-miR-4294 gene (miRBase Accession No. MIMAT0016849) set forth in SEQ ID NO: 4 and other species Homologs or orthologs and the like are included. The hsa-miR-4294 gene is described in Goff LA et al., 2009, PLoS One. , Vol. 4, e 7192. "Hsa-miR-4294" is known as "hsa-mir-4294" (miRBase Accession No. MI 0015827, SEQ ID NO: 126) which has a hairpin-like structure as its precursor.
[0091]
The term "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" as used herein refers to the hsa-miR-6729-5p gene (miRBase Accession No. MIMAT0027359), other species species homologs or orthologs, and the like. The hsa-miR-6729-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6729-5p" is known as "hsa-mir-6729" (miRBase Accession No. MI0022574, SEQ ID NO: 127) which has a hairpin- like structure as its precursor.
[0092]
As used herein, the term "hsa-miR-4476 gene" or "hsa-miR-4476" refers to the hsa-miR-4476 gene (miRBase Accession No. MIMAT 0019003) set forth in SEQ ID NO: 6 and other species Homologs or orthologs and the like are included. The hsa-miR-4476 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. Moreover, "hsa-mir-4476" (miRBase Accession No. MI 0016828, SEQ ID NO: 128) having a hairpin-like structure as its precursor is known.
[0093]
The term "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" as used herein refers to the hsa-miR-6836-3p gene (miRBase Accession No. MIMAT0027575) and other organism homologs or orthologs and the like. The hsa-miR-6836-3p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6836-3p" is known as "hsa-mir-6836" (miRBase Accession No. MI0022682, SEQ ID NO: 129) which has a hairpin-like structure as its precursor.
[0094]
The term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" as used herein refers to the hsa-miR-6765-3p gene (miRBase Accession No. 1, MIMAT0027431) and other organism homologs or orthologs and the like are included. The hsa-miR-6765-3p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6765-3p" is known as "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 130) which has a hairpin-like structure as its precursor.
[0095]
The term "hsa-miR-6799-5p gene" or "hsa-miR-6799-5p" as used herein refers to the hsa-miR-6799-5p gene (miRBase Accession No. MIMAT0027498) and other species species homologs or orthologs and the like. The hsa-miR-6799-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6799-5p" is known as "hsa-mir-6799" (miRBase Accession No. MI 00 22644, SEQ ID NO: 131) which has a hairpin-like structure as its precursor.
[0096]
The term "hsa-miR-4530 gene" or "hsa-miR-4530" as used herein refers to the hsa-miR-4530 gene (miRBase Accession No. MIMAT0019069) set forth in SEQ ID NO: 10 and other species Homologs or orthologs and the like are included. The hsa-miR-4530 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. "Hsa-miR-4530" is known as "hsa-mir-4530" (miRBase Accession No. MI 00 16897, SEQ ID NO: 132) which has a hairpin-like structure as its precursor.
[0097]
The term "hsa-miR-7641 gene" or "hsa-miR-7641" as used herein refers to the hsa-miR-7641 gene (miRBase Accession No. MIMAT0029782) set forth in SEQ ID NO: 11 and other species Homologs or orthologs and the like are included. The hsa-miR-7641 gene is described in Yoo JK et al., 2013, Arch Pharm Res. 36, p 353-358. Also, "hsa-miR-7641" is "hsa-mir-7641-1, hsa-mir-7641-2" (miRBase Accession No. MI 00 24975, MI 0024976, SEQ ID NO: 133, which is a hairpin- 134) are known.
[0098]
The term "hsa-miR-4454 gene" or "hsa-miR-4454" as used herein refers to the hsa-miR-4454 gene (miRBase Accession No. MIMAT 0018976) set forth in SEQ ID NO: 12 and other organism species Homologs or orthologs and the like are included. The hsa-miR-4454 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. Moreover, "hsa-mir-4454" (miRBase Accession No. MI 0016800, SEQ ID NO: 135) which has a hairpin-like structure as its precursor is known as "hsa-miR-4454".
[0099]
The term "hsa-miR-615-5p gene" or "hsa-miR-615-5p" as used herein refers to the hsa-miR-615-5p gene (miRBase Accession No. MIMAT0004804), other species species homologs or orthologs, and the like. The hsa-miR-615-5p gene can be obtained by the method described in Cummins JM, 2006, Proc Natl Acad Sci, 103, p. 3687-3692. Also, "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 136) which has a hairpin-like structure as its precursor is known as "hsa-miR-615-5p".
[0100]
The term "hsa-miR-8073 gene" or "hsa-miR-8073" as used herein refers to the hsa-miR-8073 gene (miRBase Accession No. MIMAT0031000) set forth in SEQ ID NO: 14 and other species Homologs or orthologs and the like are included. The hsa-miR-8073 gene is described in Wang HJ et al., 2013, Shock. , 39, p. 480-487. "Hsa-miR-8073" is known as "hsa-mir-8073" (miRBase Accession No. MI0025909, SEQ ID NO: 137) which has a hairpin-like structure as its precursor.
[0101]
The term "hsa-miR-663a gene" or "hsa-miR-663a" as used herein refers to the hsa-miR-663a gene (miRBase Accession No. MIMAT0003326) set forth in SEQ ID NO: 15 and other species Homologs or orthologs and the like are included. The hsa-miR-663a gene can be obtained by the method described in Cummins JM, 2006, Proc Natl Acad Sci, 103, p. 3687-3692. Moreover, "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 138) having a hairpin-like structure as its precursor is known as "hsa-miR-663a".
[0102]
The term "hsa-miR-4634 gene" or "hsa-miR-4634" as used herein refers to the hsa-miR-4634 gene (miRBase Accession No. MIMAT 0019691) set forth in SEQ ID NO: 16 and other organism species Homologs or orthologs and the like are included. The hsa-miR-4634 gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. Moreover, "hsa-mir-4634" (miRBase Accession No. MI 0017261, SEQ ID NO: 139) having a hairpin-like structure as its precursor is known as "hsa-miR-4634".
[0103]
The term "hsa-miR-4450 gene" or "hsa-miR-4450" as used herein refers to the hsa-miR-4450 gene (miRBase Accession No. MIMAT 0018971) set forth in SEQ ID NO: 17 and other organism species Homologs or orthologs and the like are included. The hsa-miR-4450 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. Moreover, "hsa-mir-4450" (miRBase Accession No. MI 0016795, SEQ ID NO: 140) having a hairpin-like structure as its precursor is known.
[0104]
The term "hsa-miR-4792 gene" or "hsa-miR-4792" as used herein refers to the hsa-miR-4792 gene (miRBase Accession No. MIMAT 0019964) set forth in SEQ ID NO: 18 and other species Homologs or orthologs and the like are included. The hsa-miR-4792 gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. Moreover, "hsa-mir-4792" which has a hairpin-like structure as its precursor is known (miRBase Accession No. MI 0017439, SEQ ID NO: 141).
[0105]
The term "hsa-miR-665 gene" or "hsa-miR-665" as used herein refers to the hsa-miR-665 gene (miRBase Accession No. MIMAT0004952) set forth in SEQ ID NO: 19 and other species Homologs or orthologs and the like are included. The hsa-miR-665 gene is described in Berezikov E et al., 2006, Genome Res. , Volume 16, p. 1289-1298. Moreover, "hsa-mir-665" (miRBase Accession No. M0005563, SEQ ID NO: 142) which has a hairpin-like structure as its precursor is known as "hsa-miR-665".
[0106]
The term "hsa-miR-7975 gene" or "hsa-miR-7975" as used herein refers to the hsa-miR-7975 gene (miRBase Accession No. MIMAT0031178) set forth in SEQ ID NO: 20 and other species Homologs or orthologs and the like are included. The hsa-miR-7975 gene is described in Velthut-Meikas A et al., 2013, Mol Endocrinol. Can be obtained by the method described in [Epub prior to print]. "Hsa-miR-7975" is known as "hsa-mir-7975" (miRBase Accession No. MI0025751, SEQ ID NO: 143) which has a hairpin-like structure as its precursor.
[0107]
The term "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" as used herein refers to the hsa-miR-7109-5p gene (miRBase Accession No. 1, MIMAT 0028115) and other organism homologs or orthologs and the like. The hsa-miR-7109-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-7109-5p" is known as "hsa-mir-7109" (miRBase Accession No. MI 00 22960, SEQ ID NO: 144) which has a hairpin-like structure as its precursor.
[0108]
The term "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" as used herein refers to the hsa-miR-6789-5p gene (miRBase Accession No. MIMAT0027478) and other species species homologs or orthologs and the like. The hsa-miR-6789-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6789-5p" is known as "hsa-mir-6789" (miRBase Accession No. MI 00 22634, SEQ ID NO: 145) which has a hairpin-like structure as its precursor.
[0109]
The term "hsa-miR-4497 gene" or "hsa-miR-4497" as used herein refers to the hsa-miR-4497 gene (miRBase Accession No. MIMAT0019032) set forth in SEQ ID NO: 23 and other species Homologs or orthologs and the like are included. The hsa-miR-4497 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. Moreover, "hsa-mir-4497" (miRBase Accession No. MI 0016859, SEQ ID NO: 146) which has a hairpin-like structure as its precursor is known.
[0110]
The term "hsa-miR-6877-5p gene" or "hsa-miR-6877-5p" as used herein refers to the hsa-miR-6877-5p gene (miRBase Accession No. 1, MIMAT0027654) and other organism homologs or orthologs and the like. The hsa-miR-6877-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6877-5p" is known as "hsa-mir-6877" (miRBase Accession No. MI 0022724, SEQ ID NO: 147) which has a hairpin- like structure as its precursor.
[0111]
The term "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" as used herein refers to the hsa-miR-6880-5p gene (miRBase Accession No. MIMAT0027660) and other organism homologs or orthologs and the like. The hsa-miR-6880-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa
-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 148) which has a hairpin-like structure as its precursor is known as "hsa- miR-6880-5p".
[0112]
The term "hsa-miR-7977 gene" or "hsa-miR-7977" as used herein refers to the hsa-miR-7977 gene (miRBase Accession No. MIMAT0031180) set forth in SEQ ID NO: 26 and other species Homologs or orthologs and the like are included. The hsa-miR-7977 gene is described in Velthut-Meikas A et al., 2013, Mol Endocrinol. Can be obtained by the method described in [Epub prior to print]. "Hsa-miR-7977" is known as "hsa-mir-7977" (miRBase Accession No. MI0025753, SEQ ID NO: 149) which has a hairpin-like structure as its precursor.
[0113]
The term "hsa-miR-4734 gene" or "hsa-miR-4734" as used herein refers to the hsa-miR-4734 gene (miRBase Accession No. MIMAT 0019859) set forth in SEQ ID NO: 27 and other species Homologs or orthologs and the like are included. The hsa-miR-4734 gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. Furthermore, "hsa-mir-4734" (miRBase Accession No. MI 0017371, SEQ ID NO: 150) having a hairpin-like structure as its precursor is known.
[0114]
The term "hsa-miR-6821-5p gene" or "hsa-miR-6821-5p" as used herein refers to the hsa-miR-6821-5p gene (miRBase Accession No. MIMAT0027542), other species species homologs or orthologs, and the like. The hsa-miR-6821-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6821-5p" is known as "hsa-mir-6821" (miRBase Accession No. MI0022666, SEQ ID NO: 151) which has a hairpin-like structure as its precursor.
[0115]
The term "hsa-miR-8089 gene" or "hsa-miR-8089" as used herein refers to the hsa-miR-8089 gene (miRBase Accession No. MIMAT0031016) set forth in SEQ ID NO: 29 and other species Homologs or orthologs and the like are included. The hsa-miR-8089 gene is described in Wang HJ et al., 2013, Shock. , 39, p. 480-487. "Hsa-miR-8089" is known as "hsa-mir-8089" (miRBase Accession No. MI0025925, SEQ ID NO: 152) which has a hairpin-like structure as its precursor.
[0116]
The term "hsa-miR-5585-3p gene" or "hsa-miR-5585-3p" as used herein refers to the hsa-miR-5585-3p gene (miRBase Accession No. MIMAT 0022866) and other species species homologs or orthologs and the like. The hsa-miR-5585-3p gene is described in Friedlander MR et al., 2012, Nucleic Acids Res. , Vol. 40, pp. 37-52. Also, "hsa-miR-5585-3p" is known as "hsa-mir-5585" (miRBase Accession No. MI 0019142, SEQ ID NO: 153) which has a hairpin-like structure as its precursor.
[0117]
The term "hsa-miR-6085 gene" or "hsa-miR-6085" as used herein refers to the hsa-miR-6085 gene (miRBase Accession No. MIMAT0023710) set forth in SEQ ID NO: 31 and other species Homologs or orthologs and the like are included. The hsa-miR-6085 gene is described in Voellenkle C et al., 2012, RNA. , Vol. 18, pp. 472-484. Also, "hsa-miR-6085" is known as "hsa-mir-6085" (miRBase Accession No. MI 0020362, SEQ ID NO: 154) which has a hairpin-like structure as its precursor.
[0118]
The term "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" as used herein refers to the hsa-miR-6845-5p gene (miRBase Accession No. 1, MIMAT0027590) and other organism homologs or orthologs and the like. The hsa-miR-6845-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6845-5p" is known as "hsa-mir-6845" (miRBase Accession No. MI0022691, SEQ ID NO: 155) which has a hairpin-like structure as its precursor.
[0119]
The term "hsa-miR-4651 gene" or "hsa-miR-4651" as used herein refers to the hsa-miR-4651 gene (miRBase Accession No. MIMAT 0019715) set forth in SEQ ID NO: 33 and other species Homologs or orthologs and the like are included. The hsa-miR-4651 gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. Moreover, "hsa-mir-4651" (miRBase Accession No. MI 0017279, SEQ ID NO: 156) having a hairpin-like structure as its precursor is known as "hsa-miR-4651".
[0120]
The term "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" as used herein refers to the hsa-miR-4433-3p gene (miRBase Accession No. 1, MIMAT 0018949) and other organism homologs or orthologs and the like. The hsa-miR-4433-3p gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. "Hsa-miR-4433-3p" is known as "hsa-mir-4433" (miRBase Accession No. MI 0016773, SEQ ID NO: 157) which has a hairpin-like structure as its precursor.
[0121]
The term "hsa-miR-1231 gene" or "hsa-miR-1231" as used herein refers to the hsa-miR-1231 gene (miRBase Accession No. MIMAT0005586) set forth in SEQ ID NO: 35 and other species Homologs or orthologs and the like are included. The hsa-miR-1231 gene is described in Berezikov E et al., 2007, Mol Cell. , 28, pp. 328-336. Moreover, "hsa-mir-1231" (miRBase Accession No. M0006321, SEQ ID NO: 158) having a hairpin-like structure as its precursor is known as "hsa-miR-1231".
[0122]
The term "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" as used herein refers to the hsa-miR-4665-5p gene (miRBase Accession No. MIMAT 0019739) and other species species homologs or orthologs and the like. The hsa-miR-4665-5p gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. "Hsa-miR-4665-5p" is known as "hsa-mir-4665" (miRBase Accession No. MI 0017295, SEQ ID NO: 159) which has a hairpin-like structure as its precursor.
[0123]
The term "hsa-miR-7114-5p gene" or "hsa-miR-7114-5p" as used herein refers to the hsa-miR-7114-5p gene (miRBase Accession No. MIMAT 0028125) and other species species homologs or orthologs and the like. The hsa-miR-7114-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-7114-5p" is known as "hsa-mir-7114" (miRBase Accession No. MI 00 22965, SEQ ID NO: 160) which has a hairpin-like structure as its precursor.
[0124]
The term "hsa-miR-1238-5p gene" or "hsa-miR-1238-5p" as used herein refers to the hsa-miR-1238-5p gene (miRBase Accession No. MIMAT 0022947) and other organism homologs or orthologs and the like. The hsa-miR-1238-5p gene is described in Berezikov E et al., 2007, Mol Cell. , 28, pp. 328-336. Furthermore, "hsa-mir-1238" (miRBase Accession No. M0006328, SEQ ID NO: 161) which has a hairpin-like structure as its precursor is known as "hsa-miR-1238-5p".
[0125]
As used herein, the term "hsa-miR-8069 gene" or "hsa-miR-8069" refers to the hsa-miR-8069 gene (miRBase Accession No. MIMAT0030996) set forth in SEQ ID NO: 39 and other species Homologs or orthologs and the like are included. The hsa-miR-8069 gene is described in Wang HJ et al., 2013, Shock. , 39, p. 480-487. Also, "hsa-miR-8069" is known as "hsa-mir-8069" (miRBase Accession No. MI0025905, SEQ ID NO: 162) which has a hairpin-like structure as its precursor.
[0126]
The term "hsa-miR-4732-5p gene" or "hsa-miR-4732-5p" as used herein refers to the hsa-miR-4732-5p gene (miRBase Accession No. MIMAT0019855) and other organism homologs or orthologs and the like are included. The hsa-miR-4732-5p gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. "Hsa-miR-4732-5p" is known as "hsa-mir-4732" (miRBase Accession No. MI 0017369, SEQ ID NO: 163) which has a hairpin-like structure as its precursor.
[0127]
The term "hsa-miR-619-5p gene" or "hsa-miR-619-5p" as used herein refers to the hsa-miR-619-5p gene (miRBase Accession No. MIMAT0026622) and other species species homologs or orthologs and the like. The hsa-miR-619-5p gene can be obtained by the method described in Cummins JM, 2006, Proc Natl Acad Sci, 103, p. 3687-3692. Also, "hsa-mir-619" (miRBase Accession No. MI0003633, SEQ ID NO: 164) which has a hairpin-like structure as its precursor is known as "hsa-miR-619-5p".
[0128]
The term "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" as used herein refers to the hsa-miR-3622a-5p gene (miRBase Accession No. MIMAT 0018003) and other organism homologs or orthologs and the like are included. The hsa-miR-3622a-5p gene is described in Witten D et al., 2010, BMC Biol. , Vol. 8, p. 58. "Hsa-miR-3622a-5p" is known as "hsa-mir-3622a" (miRBase Accession No. MI 0016013, SEQ ID NO: 165) which has a hairpin-like structure as its precursor.
[0129]
As used herein, the term "hsa-miR-1260a gene" or "hsa-miR-1260a" refers to the hsa-miR-1260a gene (miRBase Accession No. MIMAT0005911) set forth in SEQ ID NO: 43 and other species Homologs or orthologs and the like are included. The hsa-miR-1260a gene is described in Morin RD et al., 2008, Genome Res. , Vol. 18, p. 610-621. "Hsa-miR-1260a" is known as "hsa-mir-1260a" (miRBase Accession No. M0006394, SEQ ID NO: 166) which has a hairpin-like structure as its precursor.
[0130]
The term "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" as used herein refers to the hsa-miR-6741-5p gene (miRBase Accession No. MIMAT0027383), other species species homologs or orthologs, and the like. The hsa-miR-6741-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6741-5p" is known as "hsa-mir-6741" (miRBase Accession No. MI 00 22586, SEQ ID NO: 167) which has a hairpin-like structure as its precursor.
[0131]
The term "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" as used herein refers to the hsa-miR-6781-5p gene (miRBase Accession No. MIMAT0027462) and other organism homologs or orthologs and the like are included. The hsa-miR-6781-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6781-5p" is known as "hsa-mir-6781" (miRBase Accession No. MI0022626, SEQ ID NO: 168) which has a hairpin-like structure as its precursor.
[0132]
The term "hsa-miR-6125 gene" or "hsa-miR-6125" as used herein refers to the hsa-miR-6125 gene (miRBase Accession No. MIMAT0024598) set forth in SEQ ID NO: 46 and other species Homologs or orthologs and the like are included. The hsa-miR-6125 gene is described in Smith JL et al., 2012, J Virol. , Vol. 86, p 5278-5287. "Hsa-miR-6125" is known as "hsa-mir-6125" (miRBase Accession No. MI0021259, SEQ ID NO: 169) which has a hairpin-like structure as its precursor.
[0133]
The term "hsa-miR-6805-5p gene" or "hsa-miR-6805-5p" as used herein refers to the hsa-miR-6805-5p gene (miRBase Accession No. 1, MIMAT0027510) and other species species homologs or orthologs and the like. The hsa-miR-6805-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6805-5p" is known as "hsa-mir-6805" (miRBase Accession No. MI 00 22650, SEQ ID NO: 170) which has a hairpin-like structure as its precursor.
[0134]
The term "hsa-miR-6132 gene" or "hsa-miR-6132" as used herein refers to the hsa-miR-6132 gene (miRBase Accession No. MIMAT 0024616) set forth in SEQ ID NO: 48 and the other species Homologs or orthologs and the like are included. The hsa-miR-6132 gene is Dannemann M, 2012, Genome Biol Evol. , Vol. 4, p. 552-564. "Hsa-miR-6132" is known as "hsa-mir-6132" (miRBase Accession No. MI 0021277, SEQ ID NO: 171) which has a hairpin-like structure as its precursor.
[0135]
The term "hsa-miR-6872-3p gene" or "hsa-miR-6872-3p" as used herein refers to the hsa-miR-6872-3p gene (miRBase Accession No. MIMAT0027645), other species species homologs or orthologs, and the like. The hsa-miR-6872-3p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6872-3p" is known as "hsa-mir-6872" (miRBase Accession No. MI0022719, SEQ ID NO: 172) which has a hairpin-like structure as its precursor.
[0136]
The term "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" as used herein refers to the hsa-miR-6875-5p gene (miRBase Accession No. 1, MIMAT0027650), other species species homologs or orthologs, and the like. The hsa-miR-6875-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6875-5p" is known as "hsa-mir-6875" (miRBase Accession No. MI0022722, SEQ ID NO: 173) which has a hairpin-like structure as its precursor.
[0137]
The term "hsa-miR-1908-3p gene" or "hsa-miR-1908-3p" as used herein refers to the hsa-miR-1908-3p gene (miRBase Accession No. 1, MIMAT 0026916) and other organism homologs or orthologs and the like. The hsa-miR-1908-3p gene is described in Bar M et al., 2008, Stem Cells. , Vol. 26, p 2496-2505. "Hsa-mir-1908" (miRBase Accession No. MI0008329, SEQ ID NO: 174) which has a hairpin-like structure as its precursor is known as "hsa-miR-1908-3p".
[0138]
The term "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" as used herein refers to the hsa-miR-4433b-3p gene (miRBase Accession No. 1, MIMAT0030414), other species species homologs or orthologs, and the like. The hsa-miR-4433b-3p gene is described in Ple H et al., 2012, PLoS One. , Volume 7, e 50746. "Hsa-miR-4433b-3p" is known as "hsa-mir-4433b" (miRBase Accession No. MI0025511, SEQ ID NO: 175) having a hairpin-like structure as its precursor.
[0139]
As used herein, the term "hsa-miR-4736 gene" or "hsa-miR-4736" refers to the hsa-miR-4736 gene (miRBase Accession No. MIMAT 0019862) set forth in SEQ ID NO: 53 and other species Homologs or orthologs and the like are included. The hsa-miR-4736 gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. Moreover, "hsa-mir-4736" (miRBase Accession No. MI 0017373, SEQ ID NO: 176) having a hairpin-like structure as its precursor is known as "hsa-miR-4736".
[0140]
The term "hsa-miR-5100 gene" or "hsa-miR-5100" as used herein refers to the hsa-miR-5100 gene (miRBase Accession No. MIMAT0022259) set forth in SEQ ID NO: 54 and other species Homologs or orthologs and the like are included. The hsa-miR-5100 gene is described in Tandon M et al., 2012, Oral Dis. , 18, p. 127-131. Moreover, "hsa-mir-5100" (miRBase Accession No. MI 0019116, SEQ ID NO: 177) having a hairpin-like structure as its precursor is known as "hsa-miR-5100".
[0141]
The term "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" as used herein refers to the hsa-miR-6724-5p gene (miRBase Accession No. MIMAT0025856), other species species homologs or orthologs, and the like. The hsa-miR-6724-5p gene is described in Li Y et al., 2012, Gene. , 497, p. 330-335. "Hsa-miR-6724-5p" is known as "hsa-mir-6724" (miRBase Accession No. MI 00 22559, SEQ ID NO: 178) which has a hairpin-like structure as its precursor.
[0142]
The term "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" as used herein refers to the hsa-miR-7107-5p gene (miRBase Accession No. MIMAT 0028111) and other organism homologs or orthologs and the like are included. The hsa-miR-7107-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-7107-5p" is known as "hsa-mir-7107" (miRBase Accession No. MI0022958, SEQ ID NO: 179) which has a hairpin-like structure as its precursor.
[0143]
The term "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" as used herein refers to the hsa-miR-6726-5p gene (miRBase Accession No. MIMAT0027353) and other species species homologs or orthologs and the like. The hsa-miR-6726-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6726-5p" is known as "hsa-mir-6726" (miRBase Accession No. MI 00 22571, SEQ ID NO: 180) which has a hairpin-like structure as its precursor.
[0144]
The term "hsa-miR-3185 gene" or "hsa-miR-3185" as used herein refers to the hsa-miR-3185 gene (miRBase Accession No. MIMAT0015065) set forth in SEQ ID NO: 58 and the other species Homologs or orthologs and the like are included. The hsa-miR-3185 gene is Stark MS et al., 2010, PLoS One. , Volume 5, e 9685, which is incorporated herein by reference. "Hsa-miR-3185" is known as "hsa-mir-3185" (miRBase Accession No. MI0014227, SEQ ID NO: 181) which has a hairpin-like structure as its precursor.
[0145]
The term "hsa-miR-4638-5p gene" or "hsa-miR-4638-5p" as used herein refers to the hsa-miR-4638-5p gene (miRBase Accession No. MIMAT0019695), other species species homologs or orthologs, and the like. The hsa-miR-4638-5p gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. Also, "hsa-miR-4638-5p" is known as "hsa-mir-4638" (miRBase Accession No. MI 001726, SEQ ID NO: 182) which has a hairpin-like structure as its precursor.
[0146]
The term "hsa-miR-1273g-3p gene" or "hsa-miR-1273g-3p" as used herein refers to the hsa-miR-1273g-3p gene (miRBase Accession No. MIMAT 0022742) and other organism homologs or orthologs and the like. The hsa-miR-1273g-3p gene is described in Reshmi G et al., 2011, Genomics. , Vol. 97, p 333 - 340. "Hsa-miR-1273g-3p" is known as "hsa-mir-1273 g" (miRBase Accession No. MI 0018003, SEQ ID NO: 183) which has a hairpin-like structure as its precursor.
[0147]
The term "hsa-miR-6778-5p gene" or "hsa-miR-6778-5p" as used herein refers to the hsa-miR-6778-5p gene (miRBase Accession No. MIMAT0027456), other species species homologs or orthologs, and the like. The hsa-miR-6778-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6778-5p" is known as "hsa-mir-6778" (miRBase Accession No. MI 00 22623, SEQ ID NO: 184) which has a hairpin-like structure as its precursor.
[0148]
The term "hsa-miR-328-5p gene" or "hsa-miR-328-5p" as used herein refers to the hsa-miR-328-5p gene (miRBase Accession No. MIMAT 0026486) and other species species homologs or orthologs and the like are included. The hsa-miR-328-5p gene can be obtained by the method described in Kim J et al., 2004, Proc Natl Acad Sci, 101, p. 360-365. Also, "hsa-mir-328" (miRBase Accession No. MI 0000804, SEQ ID NO: 185) which has a hairpin-like structure as its precursor is known as "hsa-miR-328-5 p".
[0149]
The term "hsa-miR-3679-3p gene" or "hsa-miR-3679-3p" as used herein refers to the hsa-miR-3679-3p gene (miRBase Accession No. 1, MIMAT0018105) and other organism homologs or orthologs and the like are included. The hsa-miR-3679-3p gene is described in Creighton CJ et al., 2010, PLoS One. , 5th edition, e9637. "Hsa-miR-3679-3p" is known as "hsa-mir-3679" (miRBase Accession No. MI 0016080, SEQ ID NO: 186) which has a hairpin-like structure as its precursor.
[0150]
The term "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" as used herein refers to the hsa-miR-1228-3p gene (miRBase Accession No. 1, MIMAT0005583) and other organism homologs or orthologs and the like. The hsa-miR-1228-3p gene is described in Berezikov E et al., 2007, MoI Cell. , 28, pp. 328-336. Also, "hsa-miR-1228-3p" is known as "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 187) which has a hairpin-like structure as its precursor.
[0151]
The term "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" as used herein refers to the hsa-miR-6779-5p gene (miRBase Accession No. MIMAT0027458) and other organism homologs or orthologs and the like. The hsa-miR-6779-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6779-5p" is known as "hsa-mir-6779" (miRBase Accession No. MI0022624, SEQ ID NO: 188) which has a hairpin-like structure as its precursor.
[0152]
The term "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" as used herein refers to the hsa-miR-4723-5p gene (miRBase Accession No. 1, MIMAT0019838) and other species species homologs or orthologs and the like. The hsa-miR-4723-5p gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. "Hsa-miR-4723-5p" is known as "hsa-mir-4723" (miRBase Accession No. MI 0017359, SEQ ID NO: 189) having a hairpin-like structure as its precursor.
[0153]
The term "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" as used herein refers to the hsa-miR-6850-5p gene (miRBase Accession No. 1, MIMAT0027600) and other species species homologs or orthologs and the like. The hsa-miR-6850-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6850-5p" is known as "hsa-mir-6850" (miRBase Accession No. MI0022696, SEQ ID NO: 190) which has a hairpin-like structure as its precursor.
[0154]
The term "hsa-miR-760 gene" or "hsa-miR-760" as used herein refers to the hsa-miR-760 gene (miRBase Accession No. MIMAT0004957) set forth in SEQ ID NO: 68 and other organism species Homologs or orthologs and the like are included. The hsa-miR-760 gene is described in Berezikov E et al., 2006, Genome Res. , Volume 16, p. 1289-1298. Moreover, "hsa-mir-760" (miRBase Accession No. M0005567, SEQ ID NO: 191) having a hairpin-like structure as its precursor is known as "hsa-miR-760".
[0155]
The term "hsa-miR-7704 gene" or "hsa-miR-7704" as used herein refers to the hsa-miR-7704 gene (miRBase Accession No. MIMAT0030019) set forth in SEQ ID NO: 69 and other species Homologs or orthologs and the like are included. The hsa-miR-7704 gene is described in Swaminathan S et al., 2013, Biochem Biophys Res Commun. , Vol. 434, p. 228 - 234. "Hsa-miR-7704" is known as "hsa-mir-7704" (miRBase Accession No. MI0025240, SEQ ID NO: 192) which has a hairpin-like structure as its precursor.
[0156]
The term "hsa-miR-8072 gene" or "hsa-miR-8072" as used herein refers to the hsa-miR-8072 gene (miRBase Accession No. MIMAT0030999) set forth in SEQ ID NO: 70 and other species Homologs or orthologs and the like are included. The hsa-miR-8072 gene is described in Wang HJ et al., 2013, Shock. , 39, p. 480-487. "Hsa-miR-8072" is known as "hsa-mir-8072" (miRBase Accession No. MI0025908, SEQ ID NO: 193) which has a hairpin-like structure as its precursor.
[0157]
The term "hsa-miR-4486 gene" or "hsa-miR-4486" as used herein refers to the hsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) set forth in SEQ ID NO: 71 and the other species Homologs or orthologs and the like are included. The hsa-miR-4486 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. Furthermore, "hsa-mir-4486" (miRBase Accession No. MI 00 16847, SEQ ID NO: 194) having a hairpin-like structure as its precursor is known.
[0158]
The term "hsa-miR-1913 gene" or "hsa-miR-1913" as used herein refers to the hsa-miR-1913 gene (miRBase Accession No. MIMAT0007888) set forth in SEQ ID NO: 72 and other species Homologs or orthologs and the like are included. The hsa-miR-1913 gene is described in Bar M et al., 2008, Stem Cells. , Vol. 26, p 2496-2505. Furthermore, "hsa-mir-1913" (miRBase Accession No. M0008334, SEQ ID NO: 195) which has a hairpin-like structure as its precursor is known as "hsa-miR-1913".
[0159]
As used herein, the term "hsa-miR-4656 gene" or "hsa-miR-4656" refers to the hsa-miR-4656 gene (miRBase Accession No. MIMAT 0019723) set forth in SEQ ID NO: 73 and other species Homologs or orthologs and the like are included. The hsa-miR-4656 gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. "Hsa-miR-4656" is known as "hsa-mir-4656" (miRBase Accession No. MI 0017284, SEQ ID NO: 196) which has a hairpin-like structure as its precursor.
[0160]
The term "hsa-miR-1260b gene" or "hsa-miR-1260b" as used herein refers to the hsa-miR-1260b gene (miRBase Accession No. MIMAT0015041) set forth in SEQ ID NO: 74 and the other species Homologs or orthologs and the like are included. The hsa-miR-1260b gene is described in Stark MS et al., 2010, PLoS One. , Volume 5, e 9685, which is incorporated herein by reference. "Hsa-miR-1260b" is known as "hsa-mir-1260b" (miRBase Accession No. MI 0014197, SEQ ID NO: 197) which has a hairpin-like structure as its precursor.
[0161]
The term "hsa-miR-7106-5p gene" or "hsa-miR-7106-5p" as used herein refers to the hsa-miR-7106-5p gene (miRBase Accession No. MIMAT 0028109) and other species species homologs or orthologs and the like. The hsa-miR-7106-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-7106-5p" is known as "hsa-mir-7106" (miRBase Accession No. MI0022957, SEQ ID NO: 198) which has a hairpin-like structure as its precursor.
[0162]
The term "hsa-miR-6889-5p gene" or "hsa-miR-6889-5p" as used herein refers to the hsa-miR-6889-5p gene (miRBase Accession No. 1, MIMAT0027678) and other species species homologs or orthologs and the like. The hsa-miR-6889-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6889-5p" is known as "hsa-mir-6889" (miRBase Accession No. MI0022736, SEQ ID NO: 199) which has a hairpin-like structure as its precursor.
[0163]
The term "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" as used herein refers to the hsa-miR-6780b-5p gene (miRBase Accession No. 1, MIMAT0027572) and other species species homologs or orthologs and the like. The hsa-miR-6780b-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6780b-5p" is known as "hsa-mir-6780b" (miRBase Accession No. MI0022681, SEQ ID NO: 200) which has a hairpin-like structure as its precursor.
[0164]
The term "hsa-miR-6090 gene" or "hsa-miR-6090" as used herein refers to the hsa-miR-6090 gene (miRBase Accession No. MIMAT0023715) set forth in SEQ ID NO: 78 and other organism species Homologs or orthologs and the like are included. The hsa-miR-6090 gene is described in Yoo JK et al., 2013, Arch Pharm Res. 36, p 353-358. "Hsa-miR-6090" is known as "hsa-mir-6090" (miRBase Accession No. MI 0020367, SEQ ID NO: 201) which has a hairpin-like structure as its precursor.
[0165]
The term "hsa-miR-4534 gene" or "hsa-miR-4534" as used herein refers to the hsa-miR-4534 gene (miRBase Accession No. MIMAT0019073) set forth in SEQ ID NO: 79 and other species Homologs or orthologs and the like are included. The hsa-miR-4534 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. "Hsa-miR-4534" is known as "hsa-mir-4534" (miRBase Accession No. MI 0016901, SEQ ID NO: 202) which has a hairpin-like structure as its precursor.
[0166]
The term "hsa-miR-4449 gene" or "hsa-miR-4449" as used herein refers to the hsa-miR-4449 gene (miRBase Accession No. MIMAT 0018968) set forth in SEQ ID NO: 80 and other species Homologs or orthologs and the like are included. The hsa-miR-4449 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. "Hsa-mir-4449" is known as "hsa-mir-4449" (miRBase Accession No. MI 0016792, SEQ ID NO: 203) which has a hairpin-like structure as its precursor.
[0167]
The term "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" as used herein refers to the hsa-miR-5195-3p gene (miRBase Accession No. 1, MIMAT0021127) and other species species homologs or orthologs and the like. The hsa-miR-5195-3p gene is described in Schotte D et al., 2011, Leukemia. , Vol. 25, p. 139-1399. "Hsa-miR-5195-3p" is known as "hsa-mir-5195" (miRBase Accession No. MI 0018174, SEQ ID NO: 204) which has a hairpin-like structure as its precursor.
[0168]
The term "hsa-miR-1202 gene" or "hsa-miR-1202" as used herein refers to the hsa-miR-1202 gene (miRBase Accession No. MIMAT0005865) set forth in SEQ ID NO: 82 and other species Homologs or orthologs and the like are included. The hsa-miR-1202 gene is described in Marton S et al., 2008, Leukemia. , Vol. 22, described in p330-338
can be obtained by the methods Ru. Moreover, "hsa-mir-1202" (miRBase Accession No. M0006334, SEQ ID NO: 205) having a hairpin-like structure as its precursor is known as "hsa-miR-1202".
[0169]
The term "hsa-miR-4467 gene" or "hsa-miR-4467" as used herein refers to the hsa-miR-4467 gene (miRBase Accession No. MIMAT 0018994) set forth in SEQ ID NO: 83 and the other species Homologs or orthologs and the like are included. The hsa-miR-4467 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. "Hsa-miR-4467" is known as "hsa-mir-4467" (miRBase Accession No. MI 0016818, SEQ ID NO: 206) which has a hairpin-like structure as its precursor.
[0170]
The term "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" as used herein refers to the hsa-miR-6515-3p gene (miRBase Accession No. 1, MIMAT0025487) and other species species homologs or orthologs and the like. The hsa-miR-6515-3p gene is described in Joyce CE et al., 2011, Hum Mol Genet. , Vol. 20, p. 4025-4040. "Hsa-miR-6515-3p" is known as "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 207) which has a hairpin-like structure as its precursor.
[0171]
As used herein, the term "hsa-miR-4281 gene" or "hsa-miR-4281" refers to the hsa-miR-4281 gene (miRBase Accession No. MIMAT0016907) set forth in SEQ ID NO: 85 and other species Homologs or orthologs and the like are included. The hsa-miR-4281 gene is described in Goff LA et al., 2009, PLoS One. , Vol. 4, e 7192. Moreover, "hsa-mir-4281" (miRBase Accession No. MI 0015885, SEQ ID NO: 208) having a hairpin-like structure as its precursor is known as "hsa-miR-4281".
[0172]
The term "hsa-miR-4505 gene" or "hsa-miR-4505" as used herein refers to the hsa-miR-4505 gene (miRBase Accession No. MIMAT0019041) set forth in SEQ ID NO: 86 and other species Homologs or orthologs and the like are included. The hsa-miR-4505 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. "Hsa-mir-4505" is known as "hsa-mir-4505" (miRBase Accession No. MI 0016868, SEQ ID NO: 209) which has a hairpin-like structure as its precursor.
[0173]
The term "hsa-miR-4484 gene" or "hsa-miR-4484" as used herein refers to the hsa-miR-4484 gene (miRBase Accession No. MIMAT0019018) set forth in SEQ ID NO: 87 and other species Homologs or orthologs and the like are included. The hsa-miR-4484 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. "Hsa-miR-4484" is known as "hsa-mir-4484" (miRBase Accession No. MI 0016845, SEQ ID NO: 210) which has a hairpin-like structure as its precursor.
[0174]
The term "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" as used herein refers to the hsa-miR-6805-3p gene (miRBase Accession No. 1, MIMAT0027511) and other species species homologs or orthologs and the like. The hsa-miR-6805-3p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6805-3p" is known as "hsa-mir-6805" (miRBase Accession No. MI 00 22650, SEQ ID NO: 211) which has a hairpin- like structure as its precursor.
[0175]
The term "hsa-miR-3135b gene" or "hsa-miR-3135b" as used herein refers to the hsa-miR-3135b gene (miRBase Accession No. MIMAT 0018985) set forth in SEQ ID NO: 89 and other species Homologs or orthologs and the like are included. The hsa-miR-3135b gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. Moreover, "hsa-mir-3135b" (miRBase Accession No. MI 0016809, SEQ ID NO: 212) having a hairpin-like structure as its precursor is known as "hsa-miR-3135b".
[0176]
The term "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" as used herein refers to the hsa-miR-3162-5p gene (miRBase Accession No. 1, MIMAT0015036) and other organism homologs or orthologs and the like. The hsa-miR-3162-5p gene is described in Stark MS et al., 2010, PLoS One. , Volume 5, e 9685, which is incorporated herein by reference. "Hsa-miR-3162-5p" has a hairpin-like structure as its precursor "hsa-mir-3162" (miRBase Accession No. MI 0014192, SEQ ID NO: 213) is known.
[0177]
The term "hsa-miR-6768-5p gene" or "hsa-miR-6768-5p" as used herein refers to the hsa-miR-6768-5p gene (miRBase Accession No. MIMAT0027436) and other species species homologs or orthologs and the like. The hsa-miR-6768-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6768-5p" is known as "hsa-mir-6768" (miRBase Accession No. MI0022613, SEQ ID NO: 214) which has a hairpin-like structure as its precursor.
[0178]
The term "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" as used herein refers to the hsa-miR-6721-5p gene (miRBase Accession No. MIMAT0025852) and other organism homologs or orthologs and the like. The hsa-miR-6721-5p gene is described in Li Y et al., 2012, Gene. , 497, p. 330-335. Also, "hsa-miR-6721-5p" is known as "hsa-mir-6721" (miRBase Accession No. MI 00 22556, SEQ ID NO: 215) which has a hairpin-like structure as its precursor.
[0179]
The term "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" as used herein refers to the hsa-miR-1227-5p gene (miRBase Accession No. 1, MIMAT 0022941) and other organism homologs or orthologs and the like. The hsa-miR-1227-5p gene is described in Berezikov E et al., 2007 Mol Cell. , 28, pp. 328-336. "Hsa-miR-1227-5p" is known as "hsa-mir-1227" (miRBase Accession No. M0006316, SEQ ID NO: 216) which has a hairpin-like structure as its precursor.
[0180]
The term "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" as used herein refers to the hsa-miR-6722-3p gene (miRBase Accession No. MIMAT0025854) and other species species homologs or orthologs and the like. The hsa-miR-6722-3p gene is described in Li Y et al., 2012, Gene. , 497, p. 330-335. "Hsa-miR-6722-3p" is known as "hsa-mir-6722" (miRBase Accession No. MI0022557, SEQ ID NO: 217) which has a hairpin-like structure as its precursor.
[0181]
The term "hsa-miR-4286 gene" or "hsa-miR-4286" as used herein refers to the hsa-miR-4286 gene (miRBase Accession No. MIMAT0016916) set forth in SEQ ID NO: 95 and the other species Homologs or orthologs and the like are included. The hsa-miR-4286 gene is described in Goff LA et al., 2009, PLoS One. , Vol. 4, e 7192. "Hsa-miR-4286" is known as "hsa-mir-4286" (miRBase Accession No. MI 0015894, SEQ ID NO: 218) which has a hairpin-like structure as its precursor.
[0182]
The term "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" as used herein refers to the hsa-miR-4746-3p gene (miRBase Accession No. 1, MIMAT 0019881) and other organism homologs or orthologs and the like. The hsa-miR-4746-3p gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. "Hsa-miR-4746-3p" is known as "hsa-mir-4746" (miRBase Accession No. MI 0017385, SEQ ID NO: 219) which has a hairpin-like structure as its precursor.
[0183]
The term "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" as used herein refers to the hsa-miR-6727-5p gene (miRBase Accession No. 1, MIMAT0027355) and other species species homologs or orthologs and the like. The hsa-miR-6727-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. "Hsa-miR-6727-5p" is known as "hsa-mir-6727" (miRBase Accession No. MI 00 22572, SEQ ID NO: 220) which has a hairpin-like structure as its precursor.
[0184]
The term "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" as used herein refers to the hsa-miR-6816-5p gene (miRBase Accession No. MIMAT0027532) and other species species homologs or orthologs and the like. The hsa-miR-6816-5p gene is described in Ladewig E et al., 2012, Genome Res. , 22, p. 1634-1645. Also, "hsa-miR-6816-5p" is known as "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 221) which has a hairpin-like structure as its precursor.
[0185]
As used herein, the term "hsa-miR-4741 gene" or "hsa-miR-4741" refers to the hsa-miR-4741 gene (miRBase Accession No. MIMAT 0019871) set forth in SEQ ID NO: 99 and other species Homologs or orthologs and the like are included. The hsa-miR-4741 gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. Moreover, "hsa-mir-4741" (miRBase Accession No. MI 0017379, SEQ ID NO: 222) having a hairpin-like structure as its precursor is known as "hsa-miR-4741".
[0186]
The term "hsa-miR-4508 gene" or "hsa-miR-4508" as used herein refers to the hsa-miR-4508 gene (miRBase Accession No. MIMAT0019045) set forth in SEQ ID NO: 100 and the other species Homologs or orthologs and the like are included. The hsa-miR-4508 gene is described in Jima DD et al., 2010, Blood. , 116, e118-e127. Moreover, "hsa-mir-4508" (miRBase Accession No. MI 0016872, SEQ ID NO: 223) which has a hairpin-like structure as its precursor is known.
[0187]
The term "hsa-miR-940 gene" or "hsa-miR-940" as used herein refers to the hsa-miR-940 gene (miRBase Accession No. MIMAT0004983) set forth in SEQ ID NO: 101 and the other species Homologs or orthologs and the like are included. The hsa-miR-940 gene is described in Lui WO et al., 2007, A Cancer Res. , Vol. 67, p 6031-6043. Moreover, "hsa-mir-940" (miRBase Accession No. M0005762, SEQ ID NO: 224) which has a hairpin-like structure as its precursor is known as "hsa-miR-940".
[0188]
The term "hsa-miR-4327 gene" or "hsa-miR-4327" as used herein refers to the hsa-miR-4327 gene (miRBase Accession No. MIMAT0016889) set forth in SEQ ID NO: 102 and other species Homologs or orthologs and the like are included. The hsa-miR-4327 gene is described in Goff LA et al., 2009, PLoS One. , Vol. 4, e 7192. Also, "hsa-miR-4327" is known as "hsa-mir-4327" (miRBase Accession No. MI 0015867, SEQ ID NO: 225) which has a hairpin-like structure as its precursor.
[0189]
The term "hsa-miR-4665-3p gene" or "hsa-miR-4665-3p" as used herein refers to the hsa-miR-4665-3p gene (miRBase Accession No. 1, MIMAT0019740) and other species species homologs or orthologs and the like are included. The hsa-miR-4665-3p gene is described in Persson H et al., 2011, Cancer Res. , Vol. 71, p. 78-86. "Hsa-miR-4665-3p" is known as "hsa-mir-4665" (miRBase Accession No. MI 0017295, SEQ ID NO: 159) which has a hairpin- like structure as its precursor.
[0190]
The term "hsa-miR-718 gene" or "hsa-miR-718" as used herein refers to the hsa-miR-718 gene (miRBase Accession No. MIMAT0012735) set forth in SEQ ID NO: 104 and other species Homologs or orthologs and the like are included. The hsa-miR-718 gene is described in Artzi S et al., 2008, BMC Bioinformatics. , Vol. 9, p. 39. Moreover, "hsa-mir-718" (miRBase Accession No. MI 0012489, SEQ ID NO: 226) which has a hairpin-like structure as its precursor is known as "hsa-miR-718".
[0191]
The term "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" as used herein refers to the hsa-miR-125a-3p gene (miRBase Accession No. MIMAT0004602), other species species homologs or orthologs, and the like. The hsa-miR-125a-3p gene is described in Lagos-Quintana M et al., 2002, Curr Biol. , Vol. 12, p. 735-739. "Hsa-miR-125a-3p" is known as "hsa-mir-125a" (miRBase Accession No. MI 0000469, SEQ ID NO: 227) which has a hairpin-like structure as its precursor.
[0192]
The term "hsa-miR-204-3p gene" or "hsa-miR-204-3p" as used herein refers to the hsa-miR-204-3p gene (miRBase Accession No. MIMAT 0022693) and other organism homologs or orthologs and the like. The hsa-miR-204-3p gene is described in Lim LP et al., 2003, Science. , 299, p. 1540. Also, "hsa-miR-204-3p" is known as "hsa-mir-204" (miRBase Accession No. MI 0000284, SEQ ID NO: 228) which has a hairpin-like structure as its precursor.
[0193]
The term "hsa-miR-1469 gene" or "hsa-miR-1469" as used herein refers to the hsa-miR-1469 gene (miRBase Accession No. MIMAT0007347) set forth in SEQ ID NO: 107 and other species Homologs or orthologs and the like are included. The hsa-miR-1469 gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, 9, p. "Hsa-mir-1469" which has a hairpin-like structure as a precursor thereof (miRBase Accession No. M0007074, SEQ ID NO: 229) is also known.
[0194]
The term "hsa-miR-575 gene" or "hsa-miR-575" as used herein refers to the hsa-miR-575 gene (miRBase Accession No. MIMAT0003240) set forth in SEQ ID NO: 108 and other organism species Homologs or orthologs and the like are included. The hsa-miR-575 gene can be obtained by the method described in Cummins JM, 2006, Proc Natl Acad Sci, 103, p. 3687-3692. Moreover, "hsa-mir-575" (miRBase Accession No. M000582, SEQ ID NO: 230) having a hairpin-like structure as its precursor is known as "hsa-miR-575".
[0195]
The term "hsa-miR-150-3p gene" or "hsa-miR-150-3p" as used herein refers to the hsa-miR-150-3p gene (miRBase Accession No. 1, MIMAT0004610) and other organism homologs or orthologs and the like. The hsa-miR-150-3p gene is described in Lagos-Quintana M et al., 2002, Curr Biol. , Vol. 12, p. 735-739. Moreover, "hsa-mir-150" (miRBase Accession No. M 10000479, SEQ ID NO: 231) which has a hairpin-like structure as its precursor is known as "hsa-miR-150-3p".
[0196]
The term "hsa-miR-423-5p gene" or "hsa-miR-423-5p" as used herein refers to the hsa-miR-423-5p gene (miRBase Accession No. 1, MIMAT0004748) and other species species homologs or orthologs and the like. The hsa-miR-423-5p gene is described in Kasashima K et al., 2004, Biochem Biophys Res Commun. , Vol. 322, p 403-410. Also, "hsa-mir-423" (miRBase Accession No. MI0001445, SEQ ID NO: 232) which has a hairpin-like structure as its precursor is known as "hsa-miR-423-5p".
[0197]
The term "hsa-miR-564 gene" or "hsa-miR-564" as used herein refers to the hsa-miR-564 gene (miRBase Accession No. MIMAT0003228) set forth in SEQ ID NO: 111 and other species Homologs or orthologs and the like are included. The hsa-miR-564 gene can be obtained by the method described in Cummins JM, 2006, Proc Natl Acad Sci, 103, p. 3687-3692. Moreover, "hsa-mir-564" (miRBase Accession No. M000570, SEQ ID NO: 233) which has a hairpin-like structure as its precursor is known as "hsa-miR-564".
[0198]
The term "hsa-miR-3188 gene" or "hsa-miR-3188" as used herein refers to the hsa-miR-3188 gene (miRBase Accession No. MIMAT0015070) set forth in SEQ ID NO: 112 and other organism species Homologs or orthologs and the like are included. The hsa-miR-3188 gene is Stark MS et al., 2010, PLoS One. , Volume 5, e 9685, which is incorporated herein by reference. Moreover, "hsa-mir-3188" (miRBase Accession No. MI 0014232, SEQ ID NO: 234) which has a hairpin-like structure as its precursor is known as "hsa-miR-3188".
[0199]
The term "hsa-miR-1246 gene" or "hsa-miR-1246" as used herein refers to the hsa-miR-1246 gene (miRBase Accession No. MIMAT0005898) set forth in SEQ ID NO: 113 and the other species Homologs or orthologs and the like are included. The hsa-miR-1246 gene is described in Morin RD et al., 2008, Genome Res. , Vol. 18, p. 610-621. Also, "hsa-miR-1246" is known as "hsa-mir-1246" (miRBase Accession No. MI0006381, SEQ ID NO: 235) which has a hairpin-like structure as its precursor.
[0200]
As used herein, the term "hsa-miR-602 gene" or "hsa-miR-602" refers to the hsa-miR-602 gene (miRBase Accession No. MIMAT0003270) set forth in SEQ ID NO: 114 and other species Homologs or orthologs and the like are included. The hsa-miR-602 gene can be obtained by the method described in Cummins JM, 2006, Proc Natl Acad Sci, 103, p. 3687-3692. Furthermore, "hsa-mir-602" (miRBase Accession No. MI0003615, SEQ ID NO: 236) which has a hairpin-like structure as its precursor is known as "hsa-miR-602".
The scope of the claims
[Claim 1]
The pancreatic cancer markers miR-6893-5p, miR-6075, miR-6820-5p, miR-4294, miR-6729-5p, miR-4476, miR-6836-3p, miR-6765-3p, miR MiR-665, miR-7975, miR-665, miR-4575, miR- 7641, miR- 4454, miR- 615-5p, miR- 8073, miR- 663a, miR- 4634, miR- 4450, miR- 4792, miR- , MiR - 7109 - 5 p, miR - 6789 - 5 p, miR - 4497, miR - 6877 - 5 p, miR - 6880 - 5 p, miR - 7977, miR - 4734, miR - 6821 - 5 p, miR - 8089, miR - 5585 -3p, miR-6085, miR-6 MiR-473-5p, miR-4651, miR-4433-3p, miR-1231, miR- 4665-5p, miR-7114-5p, miR- 1238-5p, miR- 8069, miR- 4732-5p, miR- 619- MiR-6505-5p, miR-6132, miR-6872-3p, miR-6875-5p, miR-6872-5p, miR- miR-1727-5p, miR-1908-3p, miR-4433b-3p, miR- 4736, miR- 5100, miR-6724-5p, miR- 7107-5p, miR- 6726-5p, miR- 3185, miR- 4638-5p, miR- 1273 g - 3 p, miR - 6778 - 5 p, mi MiR - 760, miR - 7704, miR - 8072, miR - 4486, miR - 3679 - 3 p, miR - 1228 - 3 p, miR - 6779 - 5 p, miR - 4723 - 5 p, miR - 6850 - 5 p, , MiR - 1913, miR - 4656, miR - 1260 b, miR - 7106 - 5 p, miR - 6889 - 5 p, miR - 6780 b - 5 p, miR - 6090, miR - 4534, miR - 44 49, miR-5195-3p, miR-1202, miR-4467, miR-6515-3p, miR-4281, miR- 4505, miR-4484, miR-6805-3p, miR- 3135b, miR- 3162-5p, miR-6768-5p, miR-6721-5p, miR-1227-5p, miR-6722-3p, miR-4286, miR- 4746-3p, miR-6727-5p, miR- 6816-5p, miR- 4741, miR-4508, miR-940, miR-4327, miR-4665-3p, miR- 718, miR-1203, miR- 663b, miR-4258, miR- 4649-5p, miR- 4516, miR- 3619-3p, miR-6826-5p, miR-675 5p, miR-3131, miR-1343-3p, miR-6775-5p, miR-6813-5p, and miR-3940-5p specifically bindable to at least one polynucleotide selected from the group consisting of A kit for detection of pancreatic cancer containing a nucleic acid.
[Claim 2]
miR-6893-5p is hsa-miR-6893-5p, miR-6075 is hsa-miR-6075, miR-6820-5p is hsa-miR-6820-5p, miR-4294 is hsa- miR-4294, miR-6729-5p is hsa-miR-6729-5p, miR-4476 is hsa-miR-4476, miR-6836-3p is hsa-miR-6836-3p, miR-6765-3p is hsa-miR-6765-3p, miR-6799-5p is hsa-miR-6799-5p, miR-4530 is hsa-miR-4530, miR-7641 is hsa- MiR-7641, miR-4454 is hsa-miR-4454 MiR-615-5p is hsa-miR-615-5p, miR-8073 is hsa-miR-8073, miR-663a is hsa-miR-663a, miR-4634 is hsa-miR- 4634, miR - 4450 is hsa - miR - 4450, miR - 4792 is hsa - miR - 4792, miR - 665 is hsa - miR - 665, miR - 7975 is hsa - miR - 7975 MiR-7109-5p is hsa-miR-7109-5p, miR-6789-5p is hsa-miR-6789-5p, miR-4497 is hsa-miR-4497, miR-6877- 5p is hsa-miR-6877-5p, miR-6880-5 Is hsa - miR - 6880 - 5 p, miR - 7977 is hsa - miR - 7977, miR - 4734 is hsa - miR - 4734, miR - 6821 - 5 p is hsa - miR - 6821 - 5 p , MiR-8089 is hsa-miR-8089, miR-5585-3p is hsa-miR-5585-3p, miR-6085 is hsa-miR-6085, miR-6845-5 p is hsa - miR - 6845 - 5 p, miR - 4651 is hsa - miR - 4651, miR - 4433 - 3 p is hsa - miR - 4433 - 3 p, miR - 1231 is hsa - miR - 1231 Yi, miR-4665-5p is hsa-miR-4665-5p, miR-7114-5p is hsa-miR-7114-5p, miR-1238-5p is hsa-miR-1238-5p, miR-8069 is hsa-miR-8069, miR-4732-5p is hsa-miR-4732-5p, miR-619-5p is hsa-miR-619-5p, miR-3622a- hsa-miR-3622a-5p, miR-1260a is hsa-miR-12 0a, miR-6741-5p is hsa-miR-6741-5p, miR-6781-5p is hsa-miR-6781-5p, miR-6125 is hsa-miR-6125, miR- 6805-5p is hsa-miR-6805-5p, miR-6132 is hsa-miR-6132, miR-6872-3p is hsa-miR-6872-3p, miR-6875-5p is hsa- miR - 6875 - 5 p, miR - 1908 - 3 p is hsa - miR - 1908 - 3 p, miR - 4433 b - 3 p is hsa - miR - 4433 b - 3 p, miR - 4736 is hsa - miR - 4736 Yes, miR - 5100 is hsa - miR - 5100, miR - 672 -5p is hsa-miR-6724-5p, miR-7107-5p is hsa-miR-7107-5p, miR-6726-5p is hsa-miR-6726-5p, miR-3185 is hsa - miR - 3185, miR - 4638 - 5 p is hsa - miR - 4638 - 5 p, miR - 1273 g - 3 p is hsa - miR - 1273 g - 3 p, miR - 6778 - 5 p is hsa - miR -6778-5p, miR-328-5p is hsa-miR-328-5p, miR-3679-3p is hsa-miR-3679-3p, miR-1228-3p is hsa-miR-1228 -3p, miR-6779-5p is hsa-miR-6779-5p, miR-4723-5p is hsa-miR-4723-5p, miR-6850-5p is hsa-miR-6850-5p , MiR-760 is hsa-miR-760, miR-7704 is hsa-miR-7704, miR-8072 is hsa-miR-8072, miR-4486 is hsa- miR-4486 , MiR-1913 is hsa-miR-1913, miR-4656 is hsa-m R-4656, miR-1260b is hsa-miR-1260b, miR-7106-5p is hsa-miR-7106-5p, miR-6889-5p is hsa-miR-6889-5p, miR - 6780b - 5p is hsa - miR - 6780b - 5p, miR - 6090 is hsa - miR - 6090, miR - 4534 is hsa - miR - 4534, miR - 4449 is hsa - miR - 4449 MiR-5195-3p is hsa-miR-5195-3p, miR-1202 is hsa-miR-1202, miR-4467 is hsa-miR-4467, miR-6515-3p is hsa- miR-6515-3p, miR-4281 is hsa- iR - 4281, miR - 4505 is hsa - miR - 4505, miR - 4484 is hsa - miR - 4484, miR - 6805 - 3 p is hsa - miR - 6805 - 3 p, miR - 3135 b is hsa-miR-3135b, miR-3162-5p is hsa-miR-3162-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6721-5p is miR-6721-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4286 is hsa-miR- 4286, miR-4746-3p is hsa-miR-4746-3p, miR-6727-5p is hsa-miR-6727-5p, miR-6816-5p is hsa-miR-6816-5p There is miR-4341, which is hsa-miR-4741, miR-4508 is hsa-miR-4508, miR-940 is hsa-miR-940, miR-4327 is hsa-miR-4327, miR-4665-3p is hsa-miR-4665-3p, and mi -718 is hsa-miR-718, miR-1203 is hsa-miR-1203, miR-663b is hsa-miR-663b, miR-4258 is hsa-miR-4258, miR-4649 -51p is hsa-miR-4649-5p, miR-4516 is hsa-miR-4516, miR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR -6826-5p, miR-6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p , MiR-6775-5p is hsa-miR-6775-5p, m R-6813-5p is that hsa-miR-6813-5p, and, miR-3940-5p is hsa-miR-3940-5p, kit of claim 1.
[Claim 3]
(A) a polynucleotide represented by any one of the following (a) to (e):
(a) a nucleotide sequence represented by any one of SEQ ID NOS : 1 to 104, 464 to 473, and 492 to 494, A polynucleotide consisting of a nucleotide sequence in which u is t in the sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive bases,
(b) a polynucleotide consisting of the nucleotide sequence of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 ,
(C) a nucleotide sequence represented by any one of SEQ ID NOS: 1 to 104, 464 to 473, and 492 to 494 or a nucleotide sequence in which u is t in the nucleotide sequence A polynucleotide consisting of a base sequence complementary to the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases,
(d) A polynucleotide comprising a nucleotide sequence represented by any one of Nos. 1 to 104, 464 to 473, and 492 to 494 or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the nucleotide sequence, and
(e)
3. The kit according to claim 1 or 2, wherein the polynucleotide is a polynucleotide selected from the group consisting of a polynucleotide that hybridizes with the polynucleotide of any one of (a) to (d) under stringent conditions .
[Claim 4]
MiR-173p, miR-423-5p, miR-564, miR (miR- -3188, miR-1246, miR-602, miR-1290, miR-16-5p, miR-451a, miR-24-3p, miR- 187-5p, miR- 1908-5p, miR- 371a-5p and miR The kit according to any one of claims 1 to 3, further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of -550a-5p.
[Claim 5]
miR-125a-3p is hsa-miR-125a-3p, miR-204-3p is hsa-miR-204-3p, miR- 1469 is hsa-miR- 1469, miR-575 is hsa- miR-575, miR-150-3p is hsa-miR-150-3p, miR-423-5p is hsa-miR-423-5p, miR-564 is hsa- miR-564, miR - 3188 is hsa - miR - 3188, miR - 1246 is hsa - miR - 1246, miR - 602 is hsa - miR - 602, miR - 1290 is hsa - miR - 1290, miR - 16-5p is hsa-miR-16-5p, miR-451a is hsa-miR-45 ai, miR-24-3p is hsa-miR-24-3p, miR-187-5p is hsa-miR-187-5p, miR-1908-5p is hsa-miR-1908-5p 5. The kit according to claim 4, wherein miR - 371a - 5p is hsa - miR - 371a - 5p and miR - 550a - 5p is hsa - miR - 550a - 5p.
[Claim 6]
(F) a polynucleotide
represented by any one of the following (f) to (j): (f) a nucleotide sequence represented by any one of SEQ ID NOs : 105 to 122 or a nucleotide sequence in which u is t in the nucleotide sequence polynucleotide consisting, variants, derivatives thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 105 ~ 122,
(h) sequences A polynucleotide consisting of a nucleotide sequence represented by any one of the numbers 105 to 122 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a sequence comprising 15 or more consecutive bases ,
(I) a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122, or a nucleotide sequence in which u is t in the nucleotide sequence, A polynucleotide comprising a complementary nucleotide sequence, and
(j) a polynucleotide
selected from the group consisting of a polynucleotide that hybridizes with the polynucleotide of any one of (f) to (i) above under stringent conditions. 6. The kit according to claim 4 or 5, wherein
[7]
The kit according to claim 1, wherein the kit further comprises another pancreatic cancer marker, miR-4417, miR-4707-5p, miR-7847-3p, miR-2861, miR- 4513, miR-7111-5p, miR-6777-5p, miR -7113-3p, miR-4648, miR-3184-5p, miR-4271, miR-6791-5p, miR-642a-3p, miR-7108-5p, miR- 128-1-5p, miR- 5196-5p , MiR-3178, miR-3656, miR-92a-2-5p, miR-6769b-5p, miR- 4689, miR- 6076, miR-92b- 5p, miR- 6774-5p, miR-486-3p, miR -6806-5p, miR-6842-5p, miR-6716-5p, mi -557, miR-4673, miR-4674, miR-4442, miR-1915-3p, miR-4687-3p and miR-92b-3p The kit according to any one of claims 1 to 6, further comprising a bindable nucleic acid.
[Claim 8]
MiR-4417 is hsa-miR-4417, miR-4707-5p is hsa-miR-4707-5p, miR-7847-3p is hsa-miR-7847-3p, miR-2861 is hsa- miR - 2861, miR - 4513 is hsa - miR - 4513, miR - 7111 - 5 p is hsa - miR - 7111 - 5 p, miR - 6777 - 5 p is hsa - miR - 6777 - 5 p, MiR-7113-3p is hsa-miR-7113-3p, miR-4648 is hsa-miR-4648, miR-3184-5p is hsa-miR- 3184-5p, miR-4271 is hsa- miR-4271, miR-6791-5p is hsa-miR-67 MiR-642a-3p is hsa-miR-642a-3p, miR-7108-5p is hsa-miR-7108-5p, miR-128-1-5p is hsa-miR- MiR-3196-5p is hsa-miR-5196-5p, miR-3178 is hsa-miR-3178, miR-3656 is hsa-miR-3656, miR- MiR-6769b-5p is hsa-miR-6669b-5p, miR-4689 is hsa-miR-4689, miR-6076 is hsa-miR-6076, miR-92b-5p is hsa-miR-92b-5p, miR 6774-5p is hsa-miR-6774-5p, miR-486-3p is hsa-miR-486-3p, miR-6806-5p is hsa-miR-6806-5p, miR-6842- Mp-miR-6842-5p, miR-6716-5p is hsa-miR-6716-5p, miR-557 is hsa-miR-557, miR-4673 is hsa-miR-467
[Claim 9]
The polynucleotide according to any one of (k) to (o) below:
(k) a nucleotide sequence represented by any one of SEQ ID NOs : 349 to 383 or a nucleotide sequence in which u is t in the nucleotide sequence polynucleotide consisting, variants, derivatives thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (l) SEQ ID NO: 349 ~ 383,
(m) sequence A polynucleotide consisting of a nucleotide sequence represented by any one of the numbers 349 to 383 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a sequence comprising 15 or more consecutive bases a fragment thereof comprising a
phase in the base sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 349 to 383 Polynucleotide, and complementary nucleotide sequences
(o) the (k) any of the polynucleotides and polynucleotide hybridizing under stringent conditions ~ (n),
with a polynucleotide selected from the group consisting of The kit according to claim 7 or 8, which is provided.
[Claim 10]
The kit according to claim 1, wherein the kit comprises at least two or more nucleic acids capable of specifically binding to each of at least two or more polynucleotides selected from all pancreatic cancer markers according to claim 1 or 2. To (9) above.
[Claim 11]
The pancreatic cancer markers miR-6893-5p, miR-6075, miR-6820-5p, miR-4294, miR-6729-5p, miR-4476, miR-6836-3p, miR-6765-3p, miR MiR-665, miR-7975, miR-665, miR-4575, miR- 7641, miR- 4454, miR- 615-5p, miR- 8073, miR- 663a, miR- 4634, miR- 4450, miR- 4792, miR- , MiR - 7109 - 5 p, miR - 6789 - 5 p, miR - 4497, miR - 6877 - 5 p, miR - 6880 - 5 p, miR - 7977, miR - 4734, miR - 6821 - 5 p, miR - 8089, miR - 5585 -3p, miR-6085, miR-6 MiR-473-5p, miR-4651, miR-4433-3p, miR-1231, miR- 4665-5p, miR-7114-5p, miR- 1238-5p, miR- 8069, miR- 4732-5p, miR- 619- MiR-6505-5p, miR-6132, miR-6872-3p, miR-6875-5p, miR-6872-5p, miR- miR-1727-5p, miR-1908-3p, miR-4433b-3p, miR- 4736, miR- 5100, miR-6724-5p, miR- 7107-5p, miR- 6726-5p, miR- 3185, miR- 4638-5p, miR- 1273 g - 3 p, miR - 6778 - 5 p, mi MiR - 760, miR - 7704, miR - 8072, miR - 4486, miR - 3679 - 3 p, miR - 1228 - 3 p, miR - 6779 - 5 p, miR - 4723 - 5 p, miR - 6850 - 5 p, , MiR - 1913, miR - 4656, miR - 1260 b, miR - 7106 - 5 p, miR - 6889 - 5 p, miR - 6780 b - 5 p, miR - 6090, miR - 4534, miR - 44 49, miR-5195-3p, miR-1202, miR-4467, miR-6515-3p, miR-4281, miR- 4505, miR-4484, miR-6805-3p, miR- 3135b, miR- 3162-5p, miR-6768-5p, miR-6721-5p, miR-1227-5p, miR-6722-3p, miR-4286, miR- 4746-3p, miR-6727-5p, miR- 6816-5p, miR- 4741, miR-4508, miR-940, miR-4327, miR-4665-3p, miR- 718, miR-1203, miR- 663b, miR-4258, miR- 4649-5p, miR- 4516, miR- 3619-3p, miR-6826-5p, miR-675 5p, miR-3131, miR-1343-3p, miR-6775-5p, miR-6813-5p and miR-3940-5p with a nucleic acid capable of specifically binding to at least one polynucleotide selected from A device for detection, including pancreatic cancer.
[Claim 12]
miR-6893-5p is hsa-miR-6893-5p, miR-6075 is hsa-miR-6075, miR-6820-5p is hsa-miR-6820-5p, miR-4294 is hsa- miR-4294, miR-6729-5p is hsa-miR-6729-5p, miR-4476 is hsa-miR-4476, miR-6836-3p is hsa-miR-6836-3p, miR-6765-3p is hsa-miR-6765-3p, miR-6799-5p is hsa-miR-6799-5p, miR-4530 is hsa-miR-4530, miR-7641 is hsa- MiR-7641, miR-4454 is hsa-miR-4454 MiR-615-5p is hsa-miR-615-5p, miR-8073 is hsa-miR-8073, miR-663a is hsa-miR-663a, miR-4634 is hsa-miR- 4634, miR - 4450 is hsa - miR - 4450, miR - 4792 is hsa - miR - 4792, miR - 665 is hsa - miR - 665, miR - 7975 is hsa - miR - 7975 MiR-7109-5p is hsa-miR-7109-5p, miR-6789-5p is hsa-miR-6789-5p, miR-4497 is hsa-miR-4497, miR-6877- 5p is hsa-miR-6877-5p, miR-6880-5 Is hsa - miR - 6880 - 5 p, miR - 7977 is hsa - miR - 7977, miR - 4734 is hsa - miR - 4734, miR - 6821 - 5 p is hsa - miR - 6821 - 5 p , MiR-8089 is hsa-miR-8089, miR-5585-3p is hsa-miR-5585-3p, miR-6085 is hsa-miR-6085, miR-6845-5 p is hsa - miR - 6845 - 5 p, miR - 4651 is hsa - miR - 4651, miR - 4433 - 3 p is hsa - miR - 4433 - 3 p, miR - 1231 is hsa - miR - 1231 Yi, miR-4665-5p is hsa-miR-4665-5p, miR-7114-5p is hsa-miR-7114-5p, miR-1238-5p is hsa-miR-1238-5p, miR-8069 is hsa-miR-8069, miR-4732-5p is hsa-miR-4732-5p, miR-619-5p is hsa-miR-619-5p, miR-3622a- hsa-miR-3622a-5p, miR-1260a is hsa-miR-12 0a, miR-6741-5p is hsa-miR-6741-5p, miR-6781-5p is hsa-miR-6781-5p, miR-6125 is hsa-miR-6125, miR- 6805-5p is hsa-miR-6805-5p, miR-6132 is hsa-miR-6132, miR-6872-3p is hsa-miR-6872-3p, miR-6875-5p is hsa- miR - 6875 - 5 p, miR - 1908 - 3 p is hsa - miR - 1908 - 3 p, miR - 4433 b - 3 p is hsa - miR - 4433 b - 3 p, miR - 4736 is hsa - miR - 4736 Yes, miR - 5100 is hsa - miR - 5100, miR - 672 -5p is hsa-miR-6724-5p, miR-7107-5p is hsa-miR-7107-5p, miR-6726-5p is hsa-miR-6726-5p, miR-3185 is hsa - miR - 3185, miR - 4638 - 5 p is hsa - miR - 4638 - 5 p, miR - 1273 g - 3 p is hsa - miR - 1273 g - 3 p, miR - 6778 - 5 p is hsa - miR -6778-5p, miR-328-5p is hsa-miR-328-5p, miR-3679-3p is hsa-miR-3679-3p, miR-1228-3p is hsa-miR-1228 -3p, miR-6779-5p is hsa-miR-6779-5p, miR-4723-5p is hsa-miR-4723-5p, miR-6850-5p is hsa-miR-6850-5p , MiR-760 is hsa-miR-760, miR-7704 is hsa-miR-7704, miR-8072 is hsa-miR-8072, miR-4486 is hsa- miR-4486 , MiR-1913 is hsa-miR-1913, miR-4656 is hsa-m R-4656, miR-1260b is hsa-miR-1260b, miR-7106-5p is hsa-miR-7106-5p, miR-6889-5p is hsa-miR-6889-5p, miR - 6780b - 5p is hsa - miR - 6780b - 5p, miR - 6090 is hsa - miR - 6090, miR - 4534 is hsa - miR - 4534, miR - 4449 is hsa - miR - 4449 MiR-5195-3p is hsa-miR-5195-3p, miR-1202 is hsa-miR-1202, miR-4467 is hsa-miR-4467, miR-6515-3p is hsa- miR-6515-3p, miR-4281 is hsa- iR - 4281, miR - 4505 is hsa - miR - 4505, miR - 4484 is hsa - miR - 4484, miR - 6805 - 3 p is hsa - miR - 6805 - 3 p, miR - 3135 b is hsa-miR-3135b, miR-3162-5p is hsa-miR-3162-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6721-5p is miR-6721-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4286 is hsa-miR- 4286, miR-4746-3p is hsa-miR-4746-3p, miR-6727-5p is hsa-miR-6727-5p, miR-6816-5p is hsa-miR-6816-5p There is miR-4341, which is hsa-miR-4741, miR-4508 is hsa-miR-4508, miR-940 is hsa-miR-940, miR-4327 is hsa-miR-4327, miR-4665-3p is hsa-miR-4665-3p, and mi -718 is hsa-miR-718, miR-1203 is hsa-miR-1203, miR-663b is hsa-miR-663b, miR-4258 is hsa-miR-4258, miR-4649 -51p is hsa-miR-4649-5p, miR-4516 is hsa-miR-4516, miR-3619-3p is hsa-miR-3619-3p, miR-6826-5p is hsa-miR -6826-5p, miR-6757-5p is hsa-miR-6757-5p, miR-3131 is hsa-miR-3131, miR-1343-3p is hsa-miR-1343-3p , MiR-6775-5p is hsa-miR-6775-5p, m R-6813-5p is hsa-miR-6813-5p, and, miR-3940-5p is hsa-miR-3940-5p, device of claim 11.
[Claim 13]
(A) a polynucleotide represented by any one of the following (a) to (e):
(a) a nucleotide sequence represented by any one of SEQ ID NOS : 1 to 104, 464 to 473, and 492 to 494, A polynucleotide consisting of a nucleotide sequence in which u is t in the sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive bases,
(b) a polynucleotide consisting of the nucleotide sequence of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 ,
(C) a nucleotide sequence represented by any one of SEQ ID NOS: 1 to 104, 464 to 473, and 492 to 494 or a nucleotide sequence in which u is t in the nucleotide sequence A polynucleotide consisting of a base sequence complementary to the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases,
(d) A polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence represented by any one of Nos. 1 to 104, 464 to 473, and 492 to 494 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, and
(e)
Wherein the polynucleotide is a polynucleotide selected from the group consisting of a polynucleotide that hybridizes with the polynucleotide of any one of (a) to (d) under stringent conditions .
[Claim 14]
Wherein the device is selected from the group consisting of miR-125a-3p, miR-204-3p, miR-1469, miR-575, miR- 150-3p, miR-423-5p, miR-564, miR -3188, miR-1246, miR-602, miR-1290, miR-16-5p, miR-451a, miR-24-3p, miR- 187-5p, miR- 1908-5p, miR- 371a-5p and miR 14. The device according to any one of claims 11 to 13, further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of -550a-5p.
[15]
miR-125a-3p is hsa-miR-125a-3p, miR-204-3p is hsa-miR-204-3p, miR- 1469 is hsa-miR- 1469, miR-575 is hsa- miR-575, miR-150-3p is hsa-miR-150-3p, miR-423-5p is hsa-miR-423-5p, miR-564 is hsa- miR-564, miR - 3188 is hsa - miR - 3188, miR - 1246 is hsa - miR - 1246, miR - 602 is hsa - miR - 602, miR - 1290 is hsa - miR - 1290, miR - 16-5p is hsa-miR-16-5p, miR-451a is hsa-miR-45 Ai, miR-24-3p is hsa-miR-24-3p, miR-187-5p is hsa-miR-187-5p, miR-1908-5p is hsa-miR-1908-5p 15. The device according to claim 14, wherein miR - 371a - 5p is hsa - miR - 371a - 5p and miR - 550a - 5p is hsa - miR - 550a - 5p.
[Claim 16]
(F) a polynucleotide
represented by any one of the following (f) to (j): (f) a nucleotide sequence represented by any one of SEQ ID NOs : 105 to 122 or a nucleotide sequence in which u is t in the nucleotide sequence polynucleotide consisting, variants, derivatives thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 105 ~ 122,
(h) sequences A polynucleotide consisting of a nucleotide sequence represented by any one of the numbers 105 to 122 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a sequence comprising 15 or more consecutive bases ,
(I) a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122, or a nucleotide sequence in which u is t in the nucleotide sequence, A polynucleotide comprising a complementary nucleotide sequence, and
(j) a polynucleotide
selected from the group consisting of a polynucleotide that hybridizes with the polynucleotide of any one of (f) to (i) above under stringent conditions. 16. The device according to claim 14 or 15,
[Claim 17]
It said device is another pancreatic cancer marker, miR-4417, miR-4707-5p, miR-7847-3p, miR-2861, miR-4513, miR-7111-5p, miR-6777-5p, miR -7113-3p, miR-4648, miR-3184-5p, miR-4271, miR-6791-5p, miR-642a-3p, miR-7108-5p, miR-128-1-5p, miR-5196-5p , miR-3178, miR-3656, miR-92a-2-5p, miR-6769b-5p, miR-4689, miR-6076, miR-92b-5p, miR-6774-5p, miR-486-3p, miR -6806-5p, miR-6842-5p, miR-6716-5p, m R-557, miR-4673, miR-4674, miR-4442, miR-1915-3p, at least one or more polynucleotide specifically selected from the group consisting of miR-4687-3p and miR-92b-3p 17. The device according to any one of claims 11 to 16, further comprising a nucleic acid capable of binding to the target nucleic acid.
[Claim 18]
MiR-4417 is hsa-miR-4417, miR-4707-5p is hsa-miR-4707-5p, miR-7847-3p is hsa-miR-7847-3p, miR-2861 is hsa- miR - 2861, miR - 4513 is hsa - miR - 4513, miR - 7111 - 5 p is hsa - miR - 7111 - 5 p, miR - 6777 - 5 p is hsa - miR - 6777 - 5 p, MiR-7113-3p is hsa-miR-7113-3p, miR-4648 is hsa-miR-4648, miR-3184-5p is hsa-miR- 3184-5p, miR-4271 is hsa- miR-4271, miR-6791-5p is hsa-miR-67 MiR-642a-3p is hsa-miR-642a-3p, miR-7108-5p is hsa-miR-7108-5p, miR-128-1-5p is hsa-miR- MiR-3196-5p is hsa-miR-5196-5p, miR-3178 is hsa-miR-3178, miR-3656 is hsa-miR-3656, miR- MiR-6769b-5p is hsa-miR-6669b-5p, miR-4689 is hsa-miR-4689, miR-6076 is hsa-miR-6076, miR-92b-5p is hsa-miR-92b-5p, miR 6774-5p is hsa-miR-6774-5p, miR-486-3p is hsa-miR-486-3p, miR-6806-5p is hsa-miR-6806-5p, miR-6842- Mp-miR-6842-5p, miR-6716-5p is hsa-miR-6716-5p, miR-557 is hsa-miR-557, miR-4673 is hsa-miR-467
[Claim 19]
The polynucleotide according to any one of (k) to (o) below:
(k) a nucleotide sequence represented by any one of SEQ ID NOs : 349 to 383 or a nucleotide sequence in which u is t in the nucleotide sequence polynucleotide consisting, variants, derivatives thereof, or a fragment thereof comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (l) SEQ ID NO: 349 ~ 383,
(m) sequence A polynucleotide consisting of a nucleotide sequence represented by any one of the numbers 349 to 383 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a sequence comprising 15 or more consecutive bases a fragment thereof comprising a
phase in the base sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 349 to 383 Polynucleotide, and complementary nucleotide sequences
(o) the (k) any of the polynucleotides and polynucleotide hybridizing under stringent conditions ~ (n),
with a polynucleotide selected from the group consisting of 19. The device according to claim 17 or 18,
[Claim 20]
20. A device according to any one of claims 11 to 19, wherein the device is a device for measurement by hybridization technology.
[Claim 21]
21. The device of claim 20, wherein the hybridization technique is nucleic acid array technology.
[22]
The method according to claim 11, wherein the device comprises at least two or more nucleic acids capable of specifically binding to each of at least two or more polynucleotides selected from all pancreatic cancer markers according to claim 11 or 12. To (21) above.
[Claim 23]
An expression amount of a target nucleic acid in a specimen of a subject is measured using the kit according to any one of claims 1 to 10 or the device according to any one of claims 11 to 22, And the control expression level of the healthy body measured in the same manner as described above, it is evaluated in vitro that the subject is suffering from pancreatic cancer or not suffering from pancreatic cancer Method for detecting pancreatic cancer, including that.
[24]
24. The method of claim 23, wherein the subject is a human.
[Claim 25]
25. The method according to claim 23 or 24, wherein the specimen is blood, serum or plasma.
| # | Name | Date |
|---|---|---|
| 1 | Sequence listing(PDF) [20-12-2016(online)].pdf | 2016-12-20 |
| 2 | Sequence listing [20-12-2016(online)].txt | 2016-12-20 |
| 4 | PROOF OF RIGHT [20-12-2016(online)].pdf | 2016-12-20 |
| 5 | Form 5 [20-12-2016(online)].pdf | 2016-12-20 |
| 6 | Form 3 [20-12-2016(online)].pdf | 2016-12-20 |
| 7 | Form 20 [20-12-2016(online)].pdf | 2016-12-20 |
| 8 | Drawing [20-12-2016(online)].pdf | 2016-12-20 |
| 9 | Description(Complete) [20-12-2016(online)].pdf_114.pdf | 2016-12-20 |
| 10 | Description(Complete) [20-12-2016(online)].pdf | 2016-12-20 |
| 11 | Other Document [02-02-2017(online)].pdf | 2017-02-02 |
| 12 | Marked Copy [02-02-2017(online)].pdf | 2017-02-02 |
| 13 | Form 13 [02-02-2017(online)].pdf | 2017-02-02 |
| 14 | Description(Complete) [02-02-2017(online)].pdf_135.pdf | 2017-02-02 |
| 15 | Description(Complete) [02-02-2017(online)].pdf | 2017-02-02 |
| 16 | Other Patent Document [07-03-2017(online)].pdf | 2017-03-07 |
| 17 | Information under section 8(2) [12-06-2017(online)].pdf | 2017-06-12 |
| 18 | 201637043465-MARKED COPIES OF AMENDEMENTS [15-11-2017(online)].pdf | 2017-11-15 |
| 19 | 201637043465-AMMENDED DOCUMENTS [15-11-2017(online)].pdf | 2017-11-15 |
| 20 | 201637043465-Amendment Of Application Before Grant - Form 13 [15-11-2017(online)].pdf | 2017-11-15 |
| 21 | 201637043465-FORM 18 [28-05-2018(online)].pdf | 2018-05-28 |
| 22 | 201637043465-MARKED COPIES OF AMENDEMENTS [30-05-2018(online)].pdf | 2018-05-30 |
| 23 | 201637043465-AMMENDED DOCUMENTS [30-05-2018(online)].pdf | 2018-05-30 |
| 24 | 201637043465-Amendment Of Application Before Grant - Form 13 [30-05-2018(online)].pdf | 2018-05-30 |
| 25 | 201637043465-FORM-26 [28-09-2018(online)].pdf | 2018-09-28 |
| 26 | 201637043465-Information under section 8(2) (MANDATORY) [07-11-2019(online)].pdf | 2019-11-07 |
| 27 | 201637043465-FER.pdf | 2021-10-18 |
| 28 | 201637043465-AbandonedLetter.pdf | 2024-06-07 |
| 1 | strategy_43465E_30-09-2021.pdf |