Abstract: Provided are an esophageal cancer detection kit or device and an esophageal cancer detection method. An esophageal cancer detection kit or device including a nucleic acid capable of bonding specifically with miRNA in a subject specimen and an esophageal cancer detection method including measuring the miRNA in vitro.
The present invention is used for inspection of the presence or absence of diseased to esophageal cancer in a subject, the detection kit or device of esophageal cancer, including specific miRNA specifically bindable nucleic acid and the nucleic acid a method for detecting esophageal cancer comprising measuring the expression level of the miRNA with.
Background technique
[0002]
Esophagus is a tubular organ to send the food from the mouth to the stomach, it is located between the trachea and spine. The wall of the esophagus is responsible mucosa from the inside toward the outside, submucosa, muscularis propria, is divided into four layers of the outer membrane, a function for sending the food from the mouth to the stomach, respectively (Non-Patent Document 1) . When the National Research and Development Institute of the National Cancer Research Center for Cancer Control and Information Center According to the statistics of the site-specific cancer in 2012 in Japan to disclose, the number of deaths due to esophageal cancer is up to 11,592 people, site-specific a tenth of cancer cause of death. In addition, the risk of death from esophageal cancer in Japan, it is 5.6 times higher than women in men, also, smoking and alcohol intake is a risk factor for esophageal cancer (Non-Patent Document 1). In addition, in the United States, one in every 125 people in the men, women are said to develop esophageal cancer at a rate of one in 435 people, estimated esophageal cancer sufferers number of 2014 to 18,170 people also up, of which about 15,450 people is to die (non-Patent Document 1).
[0003]
The degree of progress of the esophageal cancer is defined in the Non-Patent Document 2, the size of the tumor (Tis, T1 ~ 3 and T4a ~ b), lymph node metastasis (N1 ~ 3), distant metastasis (M0 ~ 1), etc. by stage 0 (Tis / N0 / M0), stage IA (T1 / N0 / M0), stage IB (T2 / N0 / M0), stage IIA (T3 / N0 / M0), stage IIB (T1 ~ 2 / N1 / M0), stage IIIA (T4a / N0 / M0, T3 / N1 / M0, and, T1 ~ 2 / N2 / M0), stage IIIB (T3 / N2 / M0), stage IIIC (T4a / N1 ~ 2 / M0, T4b / M 0, and, N3 / M 0), and are classified into the stage IV (M1).
[0004]
5-year relative survival rate of esophageal cancer is highly dependent on the degree of progress of the cancer, 39 percent in the cancer that was confined to the esophageal tissue, 21% in the cancer that has remained until the adjacent tissue, in a cancer that has distant metastases It is reported to be 4% (non-Patent Document 1). Therefore, since finding the esophageal cancer at an early stage leads to significant improvements in survival rates, the provision of means enabling early detection has been desired strongly.
[0005]
Treatment of esophageal cancer, is determined from the degree of progress and the general condition of cancer, mainly endoscopic therapy, surgery, there is radiation therapy and anti-cancer agents. In some extent advanced cancer, multidisciplinary therapy to produce a synergistic effect while taking the characteristics of each combination of these treatments is carried out (Non-Patent Document 1). The stage 0 and at the early esophageal cancer, such as 1, may endoscope less burden on the patient treatment and photodynamic treatment may be adaptive (non-patent document 1).
[0006]
According to Non-Patent Document 1, a general examination of the esophageal cancer is esophageal angiography and endoscopy according to X-ray. CT examination in order to see the degree of spread of the cancer to other, MRI examination, endoscopic ultrasound, and ultrasound examination is carried out. If the findings esophageal cancer is suspected came out in these primary examination, the lesion to stab the needle to collect cells and tissues as a secondary inspection to implement the pathological examination examine under a microscope. Further, the blood tumor markers for esophageal cancer detection, for example, CEA and SCC is known (Non-Patent Document 3).
[0007]
Albeit at the research stage, as shown in Patent Document 1, it is combined with the expression level of the expression level, or miRNA expression level and other protein markers of micro RNA in a biological sample, including blood (miRNA) by, there is a report that detects esophageal cancer.
[0008]
Patent Document 1, miR-663a in the serum, miR-92a-3p, measuring the miRNA, such as miR-575, a method for detecting esophageal cancer is shown.
CITATION
Patent literature
[0009]
Patent Document 1: US Patent Application Publication No. 2014/031246 Pat.
Non-patent literature
[0010]
Non-Patent Document 1: American Cancer Society, "Esophagus Cancer", 2014 Supervisor, p. 2 ~ 41 ~ 20,29 ~ 8,19
Non-Patent Document 2: Sobin, L. Ra, "TNM Classification of Malignant Tumours 7th edition Japanese version of" 2009, p. 63 to 68
Non-Patent Document 3: Terada, T. Ra, 2013, International Journal of Clinical and Experimental Medicine , Section 6 (3) Volume, p. 219-26
Summary of the invention
Problems that the Invention is to Solve
[0011]
An object of the present invention is to find a novel esophageal cancer tumor marker is to provide a method capable of effectively detecting esophageal cancer using specifically capable of binding the nucleic acid to said marker.
[0012]
As described in Non-Patent Document 1, a general examination of the esophageal cancer is esophageal angiography and endoscopy according to X-ray. However for normal examination focuses on examination of stomach cancer, esophagus are often not sufficiently observed. In addition, even today that these tests have been spread in general, the number of deaths due to cancer of the esophagus of the home country is steadily increasing, not necessarily the image diagnosis is possible to suppress the esophageal cancer. Moreover, CT examination or MRI examination, although it is possible to detect the esophageal cancer in high-performance, it requires special equipment, for testing costs are expensive, not suitable to spread widely as a primary test it is.
[0013]
The blood tumor markers for esophageal cancer detection, for example, but such as CEA and SCC is known (Non-Patent Document 3), etc. These markers rise in cancers other than esophageal cancer, accuracy since there is the above considerations, its usefulness has not been established. By If the use of these markers, if the other cancer was misdiagnosed as esophageal cancer, or missed the opportunity of appropriate treatment, wrong will be applied to medical care, unnecessary in patients economic, physical fitness burden It will be have strength. Therefore, there is no description of these markers to guide of esophageal cancer of the American Cancer Society (Non-Patent Document 1).
[0014]
Although reports that albeit at the research stage to determine the esophageal cancer using the expression level of a micro RNA in a biological sample, including blood (miRNAs) are in the following, none of put to practical use.
[0015]
Patent Document 1, miR-663a in the serum, miR-92a-3p, measuring the miRNA, such as miR-575, a method for detecting esophageal cancer is shown. Specifically, compared with healthy subjects 12 patients have been shown miRNA list that varies sera of esophageal cancer patients 16 people, and measuring the expression level of the miRNA, to determine whether esophageal cancer. However, this detection method is specific accuracy to determine the esophageal cancer, sensitivity, examples, and there is almost no description of the detection performance of such specificity, poor industrial practicality. Only has been verified hsa-miR-345 is AUC is 0.814, there is also a description that it is difficult to determine esophageal cancer alone.
[0016]
Thus, in the detection of esophageal cancer, either because an existing tumor markers its performance is low, or the marker research stage method of performance and detection is not specifically shown, when utilizing these is, a healthy body and the implementation of useless additional testing due to the erroneous detection and esophagus cancer patients, there is a possibility that the loss occurs in the therapeutic opportunity by overlooking the esophageal cancer patients. Further, since it is increasing the inspection costs of measuring miRNA consisting of several tens to several hundreds, difficult to use for large-scale screening, such as medical examination. In addition, because of the high undesirable invasive to the patient is taking a esophageal tissue to measure the tumor marker, it can be detected from the blood that can be collected in a minimally invasive, and esophageal cancer esophageal cancer patients as a patient, also a healthy body as a healthy body, can be correctly determined, high esophageal cancer marker of accuracy is required. In particular, esophageal cancer is to be found in the early treatment, the survival rate can be greatly improved, also to be able to adapt a small endoscopic therapy or photodynamic therapy of the burden to the patient in the treatment selection from becoming higher esophageal cancer marker sensitivity which can be detected even at a low esophageal cancer progression degree is desired.
Means for Solving the Problems
[0017]
The present inventors have result of intensive studies to solve the above problems, the blood found several genes that can be used to detect marker esophageal cancer from the use specifically capable of binding nucleic acids thereto, esophagus It found that cancer can be significantly detected, thereby completing the present invention.
In other words, the present invention has the following features.
(1) it is an esophageal cancer marker, miR-204-3p, miR-1247-3p , miR-6875-5p, miR-6857-5p, miR-6726-5p, miR-3188, miR-8069, miR- 4257, miR-1343-3p, miR- 7108-5p, miR-6825-5p, miR-7641, miR-3185, miR-4746-3p, miR-6791-5p, miR-6893-5p, miR-4433b- 3p, miR-3135b, miR- 6781-5p, miR-1908-5p, miR-4792, miR-7845-5p, miR-4417, miR-3184-5p, miR-1225-5p, miR-1231, miR- 1225-3p, miR-150-3p, miR- 4433-3p, miR-6125, miR-4513, miR-6787-5p, miR-6784-5p, miR-615-5p, miR-6765-3p, miR- 5572, miR-6842-5p, miR- 8063, miR-6780b-5p, miR-187-5p, miR-128-1-5p, miR-6729-5p, miR-6741-5p, miR-6757-5p, miR-7110-5p, miR-7975, miR-1233-5p, miR-6845-5p, miR-3937, miR-4467, miR-7109-5p, miR-6088, miR-6782-5p, miR-5195- 3p, miR-4454, miR- 6724-5p, miR-8072, miR-4516, miR-6756-5p, miR-4665-3p, miR-6826-5p, miR-6820-5p, miR-6887-5p, miR-3679-5p, miR-7847-3p, miR-6721-5p, miR-3622a-5p, miR-939-5p, miR-602, miR-7977, miR-6749-5p, miR-1914-3p, miR-4651, miR-4695-5p, miR-6848-5p, miR-1228-3p, miR-642b-3p, miR-6746-5p, miR-3620-5p, miR-3131, miR-6732-5p, miR-7113-3p, miR-23a- 3p, miR-3154, miR-4723-5p, miR-3663-3p, miR-4734, miR-6816-5p, miR-4442, miR-4476, miR-423- 5p, miR-1249, miR- 6515-3p, miR-887-3p, miR-4741, miR-6766-3p, miR-4673, miR-6779-5p, miR-4706, miR-1268b, miR-4632- 5p, miR-3197, miR- 6798-5p, miR-711, miR-6840-3p, miR-6763-5p, miR-6727-5p, miR-371a-5p, miR-6824-5p, miR-4648, miR-1227-5p, miR-564, miR-3679-3p, miR-2861, miR-6737-5p, miR-4725-3p, miR-6716-5p, miR-4675, miR-1915-3p, miR- 671-5p, miR-3656, miR- 6722-3p, miR-4707-5p, miR-4449, miR-1202, miR-4649-5p, miR-744-5p, miR-642a-3p, miR-451a, miR-6870-5p, miR-4443, miR-6808-5p, miR-4728-5p, miR-937-5p, miR-135a-3p, miR-663b, miR-1343-5p, miR-6822-5p, miR-6803-5p, miR-6805-3p, miR-128-2-5p, miR-4640-5p, miR-1469, miR-92a-2-5p, miR-3940-5p, miR-4281, miR- 1260b, miR-4758-5p, miR- 1915-5p, miR-5001-5p, miR-4286, miR-6126, miR-6789-5p, miR-4459, miR-1268a, miR-6752-5p, miR- 6131, miR-6800-5p, miR- 4532, miR-6872-3p, miR-718, miR-6769a-5p, miR-4707-3p, miR-6765-5p, miR-4739, miR-4525, miR- 4270, miR-4534, miR- 6785-5p, miR-6850-5p, miR-4697-5p, miR-1260a, miR-4486, miR-6880-5p, miR-6802-5p, miR-6861-5p, miR-92b-5p, miR- 1238-5p, miR-6851-5p, miR-7704, miR-149-3p, miR-4689, miR-4688, miR-125a-3p, miR-23b-3p, miR- 614, miR-1913, miR- 16-5p, miR-6717-5p, miR-3648, miR-3162-5p, miR-1909-3p, miR-8073, miR-6769b-5p, miR-6836-3p, miR-4484, miR-6819-5p and at least one polynucleotide that specifically comprising bondable nucleic acid detection kit for esophageal cancer is selected from the group consisting of miR-6794-5p.
(2) miR-204-3p is hsa-miR-204-3p, miR- 1247-3p is hsa-miR-1247-3p, miR- 6875-5p is located in the hsa-miR-6875-5p , miR-6857-5p is hsa-miR-6857-5p, miR- 6726-5p is hsa-miR-6726-5p, miR- 3188 is hsa-miR-3188, is miR-8069 hsa a -miR-8069, miR-4257 is hsa-miR-4257, miR- 1343-3p is hsa-miR-1343-3p, miR- 7108-5p is located in the hsa-miR-7108-5p , miR-6825-5p is hsa-miR-6825-5p, miR- 7641 is hsa-miR-7641, miR- 3185 is hsa-miR-3185, miR- 4746-3p is hsa-miR a -4746-3p, miR-6791-5p is hsa-miR-6791-5p, miR- 6893-5p is hsa-miR-6893-5p, miR- 4433b-3p is hsa-miR-4433b a -3p, miR-3135b is hsa-miR-3135b, miR- 6781-5p is hsa-miR-6781-5p, miR- 1908-5p is hsa-miR-1908-5p, miR -4792 is hsa-miR-4792, miR- 7845-5p is hsa-miR-7845-5p, miR- 4417 is hsa-miR-4417, miR- 3184-5p is hsa-miR-3184 a -5p, miR-1225-5p is hsa-miR-1225-5p, miR- 1231 is hsa-miR-1231, miR- 1225-3p is hsa-miR-1225-3p, miR -150-3p is hsa-miR-150-3p, miR- 4433-3p is hsa-miR-4433-3p, miR- 6125 is hsa-miR-6125, miR- 4513 is hsa-miR is -4513, miR-6787-5p is hsa-miR-6787-5p, miR- 6784-5p is hsa-miR-6784-5p, miR- 615-5p is hsa-miR-615-5p at is, miR-6765-3p is hsa-miR-6765-3p, miR- 5572 is hsa-miR-5572, miR- 6842-5p is hsa-miR-6842-5p, miR- 8063 there is a hsa-miR-8063, miR- 6780b-5p is hsa-miR-6780b-5p, miR-187-5p is hsa-miR-187-5p, miR- 128-1-5p is hsa a -miR-128-1-5p, miR-6729-5p is hsa-miR-6729-5p, miR- 6741-5p is hsa-miR-6741-5p, the miR-6757-5p hsa -miR-6757-5p is, miR-7110-5p is hsa-miR-7110-5p, miR- 7975 is hsa-miR-7975, miR- 1233-5p is hsa-miR-1233-5p at is, miR-6845-5p is hsa-miR-6845-5p, miR- 3937 is hsa-miR-3937, miR- 4467 is hsa-miR-4467, miR- 7109-5p is hsa -miR-7109-5p is, miR-6088 is hsa-miR-6088, miR- 6782-5p is hsa-miR-6782-5p, miR- 5195-3p is hsa-miR-5195-3p at is, miR-4454 is hsa-miR-4454, miR- 6724-5p is hsa-miR-6724-5p, miR- 8072 is hsa-miR-8072, miR- 4516 is hsa-miR is -4516, miR-6756-5p is hsa-miR-6756-5p, miR- 4665-3p is hsa-miR-4665-3p, miR- 6826-5p is hsa-miR-6826-5p at is, miR-6820-5p is hsa-miR-6820-5p, miR- 6887-5p is hsa-miR-6887-5p, miR- 3679-5p is located in the hsa-miR-3679-5p , miR-7847-3p is hsa-miR-7847-3p, miR- 6721-5p is hsa-miR-6721-5p, miR- 3622a-5p is hsa-miR-3622a-5p, miR -939-5p is hsa-miR-939-5p, miR- 602 is hsa-miR-602, miR- 7977 is hsa-miR-7977, miR- 6749-5p is hsa-miR-6749 a -5p, miR-1914-3p is hsa-miR-1914-3p, miR- 4651 is hsa-miR-4651, miR- 4695-5p is hsa-miR-4695-5p, miR -6848-5p is hsa-miR-6848-5p, miR- 1228-3p is hsa-miR-1228-3p, miR- 642b-3p is hsa-miR-642b-3p, miR-6746 -5p is hsa-miR-6746-5p, miR- 3620-5p is hsa-miR-3620-5p, miR- 3131 is hsa-miR-3131, miR- 6732-5p is hsa-miR a -6732-5p, miR-7113-3p is hsa-miR-7113-3p, miR- 23a-3p is hsa-miR-23a-3p, miR-3154 is located in the hsa-miR-3154 , miR-4723-5p is hsa-miR-4723-5p, miR- 3663-3p is hsa-miR-3663-3p, miR- 4734 is hsa-miR-4734, miR- 6816-5p There is a hsa-miR-6816-5p, miR- 4442 is hsa-miR-4442, miR- 4476 is hsa-miR-4476, miR- 423-5p is located in the hsa-miR-423-5p , miR-1249 is hsa-miR-1249, miR- 6515-3p is hsa-miR-6515-3p, miR- 887-3p is hsa-miR-887-3p, is miR-4741 hsa a -miR-4741, miR-6766-3p is hsa-miR-6766-3p, miR- 4673 is hsa-miR-4673, miR- 6779-5p is located in the hsa-miR-6779-5p , miR-4706 is hsa-miR-4706, miR- 1268b is hsa-miR-1268b, miR- 4632-5p is hsa-miR-4632-5p, miR- 3197 is hsa-miR-3197 at is, miR-6798-5p is hsa-miR-6798-5p, miR- 711 is hsa-miR-711, miR- 6840-3p is hsa-miR-6840-3p, miR- 6763 -5p is hsa-miR-6763-5p, miR- 6727-5p is hsa-miR-6727-5p, miR- 371a-5p is hsa-miR-371a-5p, miR-6824-5p There is a hsa-miR-6824-5p, miR- 4648 is hsa-miR-4648, miR- 1227-5p is hsa-miR-1227-5p, miR- 564 is located in the hsa-miR-564 , miR-3679-3p is hsa-miR-3679-3p, miR- 2861 is hsa-miR-2861, miR- 6737-5p is hsa-miR-6737-5p, miR- 4725-3p there is a hsa-miR-4725-3p, miR- 6716-5p is hsa-miR-6716-5p, miR- 4675 is hsa-miR-4675, miR- 1915-3p is hsa-miR-1915 a -3p, miR-671-5p is hsa-miR-671-5p, miR- 3656 is hsa-miR-3656, miR- 6722-3p is hsa-miR-6722-3p, miR -4707-5p is hsa-miR-4707-5p, miR- 4449 is hsa-miR-4449, miR- 1202 is hsa-miR-1202, miR- 4649-5p is hsa-miR-4649 a -5p, miR-744-5p is hsa-miR-744-5p, miR- 642a-3p is hsa-miR-642a-3p, miR-451a is hsa-miR-451a, miR -6870-5p is hsa-miR-6870-5p, miR- 4443 is hsa-miR-4443, miR- 6808-5p is hsa-miR-6808-5p, miR- 4728-5p is hsa -miR-4728-5p is, miR-937-5p is hsa-miR-937-5p, miR- 135a-3p is hsa-miR-135a-3p, miR-663b is hsa-miR-663b at is, miR-1343-5p is hsa-miR-1343-5p, miR- 6822-5p is hsa-miR-6822-5p, miR- 6803-5p is located in the hsa-miR-6803-5p , miR-6805-3p is hsa-miR-6805-3p, miR- 128-2-5p is hsa-miR-128-2-5p, miR- 4640-5p is hsa-miR-4640-5p at is, miR-1469 is hsa-miR-1469, miR- 92a-2-5p is hsa-miR-92a-2-5p, miR-3940-5p is located in the hsa-miR-3940-5p , miR-4281 is hsa-miR-4281, miR- 1260b is hsa-miR-1260b, miR- 4758-5p is hsa-miR-4758-5p, miR- 1915-5p is hsa-miR a -1915-5p, miR-5001-5p is hsa-miR-5001-5p, miR- 4286 is hsa-miR-4286, miR- 6126 is hsa-miR-6126, miR- 6789 -5p is hsa-miR-6789-5p, miR- 4459 is hsa-miR-4459, miR- 1268a is hsa-miR-1268a, miR- 6752-5p is hsa-miR-6752-5p at is, miR-6131 is hsa-miR-6131, miR- 6800-5p is hsa-miR-6800-5p, miR- 4532 is hsa-miR-4532, miR- 6872-3p is hsa -miR-6872-3p is, miR-718 is hsa-miR-718, miR- 6769a-5p is hsa-miR-6769a-5p, miR-4707-3p is hsa-miR-4707-3p at is, miR-6765-5p is hsa-miR-6765-5p, miR- 4739 is hsa-miR-4739, miR- 4525 is hsa-miR-4525, miR- 4270 is hsa-miR is -4270, miR-4534 is hsa-miR-4534, miR- 6785-5p is hsa-miR-6785-5p, miR- 6850-5p is hsa-miR-6850-5p, miR -4697-5p is hsa-miR-4697-5p, miR- 1260a is hsa-miR-1260a, miR- 4486 is hsa-miR-4486, miR- 6880-5p is hsa-miR-6880 a -5p, miR-6802-5p is hsa-miR-6802-5p, miR- 6861-5p is hsa-miR-6861-5p, miR- 92b-5p is hsa-miR-92b-5p is
in, miR-1 238-5P is the hsa-miR-1238-5p, miR- 6851-5p is hsa-miR-6851-5p, miR- 7704 is hsa-miR-7704, miR- 149-3p is hsa-miR-149-3p, miR- 4689 is hsa-miR-4689, miR- 4688 is hsa-miR-4688, miR- 125a-3p is hsa-miR-125a- is 3p, miR-23b-3p is hsa-miR-23b-3p, miR-614 is hsa-miR-614, miR- 1913 is hsa-miR-1913, is miR-16-5p is hsa-miR-16-5p, miR- 6717-5p is hsa-miR-6717-5p, miR- 3648 is hsa-miR-3648, miR- 3162-5p is hsa-miR-3162- a 5p, miR-1909-3p is hsa-miR-1909-3p, miR- 8073 is hsa-miR-8073, miR- 6769b-5p is hsa-miR-6769b-5p, miR- 6836-3p is hsa-miR-6836-3p, miR- 4484 is hsa-miR-4484, miR- 6819-5p is hsa-miR-6819-5p, and, the miR-6794-5p is hsa-miR-6794-5p, kit according to (1).
(3) said nucleic acid, a polynucleotide shown in the following (a) -
(e): (a) SEQ ID NO: 1 to 115 and 117 to 189, and the base sequence or the represented by any one of 666-675 polynucleotides, a variant thereof comprising the nucleotide sequence u is t in the nucleotide sequence, the fragment comprising the derivative, or 15 or more contiguous
bases, (b) SEQ ID NOs 115 and 117 to 189, and, 666 a polynucleotide comprising the nucleotide sequence represented by any one of 675
~, (c) SEQ ID NOs 115 and 117 to 189, and, u is the nucleotide sequence or the nucleotide sequence represented by any one of 666-675 polynucleotides, a variant thereof comprising a nucleotide sequence complementary to the nucleotide sequence which is t, the fragment comprising the derivative, or 15 or more contiguous bases,
(d-) SEQ ID NOs 115 and 117 to 189 and, 666 polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 675, and
any one of (e) above (a) ~ (d) polynucleotide and a polynucleotide hybridizing under stringent conditions,
the kit is a polynucleotide selected from the group consisting of, according to (1) or (2).
(4) the kit further comprises a polynucleotide capable of specifically binding nucleic acids consisting of miR-575 and miR-24-3p, another esophageal cancer marker, any one of (1) to (3) the kit according to.
(5) miR-575 is hsa-miR-575, miR- 24-3p is hsa-miR-24-3p, kit according to (4).
(6) said nucleic acid, a polynucleotide shown in the following (f) ~ (j):
the nucleotide sequence u is t in (f) the nucleotide sequence or the nucleotide sequence represented by SEQ ID NO: 116 and 676 poly nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides,
polynucleotides, comprising the nucleotide sequence represented by (g) SEQ ID NO: 116 and 676 tables in (h) SEQ ID NO: 116 and 676 is the nucleotide sequence or polynucleotide having a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous nucleotides,
(i) sequences polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by numbers 116 and 676, and
one of poly (j) wherein (f) ~ (i) nucleotides under stringent conditions hybridizing polynucleotide,
a polynucleotide selected from the group consisting of a kit according to (4) or (5).
(7) The kit is another of esophageal cancer marker, miR-675-5p, miR-486-3p , miR-6777-5p, miR-4497, miR-296-3p, miR-6738-5p, miR-4731-5p, miR-6889-5p, miR-6786-5p, miR-92a-3p, miR-4294, miR-4763-3p, miR-6076, miR-663a, miR-760, miR-4667- 5p, is selected from miR-6090, miR-4730, miR-7106-5p, miR-3196, miR-5698, miR-6087, miR-4665-5p, the group consisting of miR-8059 and miR-6879-5p further comprising at least one polynucleotide capable of specifically binding nucleic acids, the kit according to any one of (1) to (6).
(8) miR-675-5p is hsa-miR-675-5p, miR- 486-3p is hsa-miR-486-3p, miR- 6777-5p is located in the hsa-miR-6777-5p , miR-4497 is hsa-miR-4497, miR- 296-3p is hsa-miR-296-3p, miR- 6738-5p is hsa-miR-6738-5p, miR- 4731-5p there is a hsa-miR-4731-5p, miR- 6889-5p is hsa-miR-6889-5p, miR- 6786-5p is hsa-miR-6786-5p, miR- 92a-3p is hsa a -miR-92a-3p, miR- 4294 is hsa-miR-4294, miR- 4763-3p is hsa-miR-4763-3p, miR- 6076 is hsa-miR-6076, miR -663a is hsa-miR-663a, miR- 760 is hsa-miR-760, miR- 4667-5p is hsa-miR-4667-5p, miR- 6090 is located in the hsa-miR-6090 , miR-4730 is hsa-miR-4730, miR- 7106-5p is hsa-miR-7106-5p, miR- 3196 is hsa-miR-3196, miR- 5698 is hsa-miR-5698であり、miR-6087がhsa-miR-6087であり、miR-4665-5pがhsa-miR-4665-5pであり、miR-8059がhsa-miR-8059であり、及び、miR-6879-5pがhsa-miR-6879-5pである、(7)に記載のキット。
[0018]
Nucleotide, polynucleotide, DNA, by abbreviations such as RNA shall be in accordance with customary in the "Guidelines for the creation of specification and the like, including the nucleotide sequence or amino acid sequence" (Japan Patent Office ed.) And the art .
[0019]
A "polynucleotide" as used herein, RNA, DNA, and none of the RNA / DNA (chimeric) used for encompasses nucleic acids. Incidentally, the above-mentioned DNA, include cDNA, genomic DNA, and even synthetic DNA is. Also included in the above RNA, total RNA, include mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, none of the non-coding (non-coding) RNA and synthetic RNA are. "Synthetic DNA" and "synthetic RNA" as used herein based on the predetermined nucleotide sequence (either the native sequence or non-naturally occurring sequence good.), For example using an automated nucleic acid synthesizer, artificially It refers fabricated DNA and RNA. "Non-naturally occurring sequence" as used herein, are intended to be used in the broad sense, differs from the native sequence, e.g., one or more nucleotide substitutions, deletions, insertions and / or sequence comprising an additional encompasses (i.e., mutated sequence), the sequence comprising one or more modified nucleotides (i.e., a modified sequence), and the like. In this description, a polynucleotide is used interchangeably with nucleic acid.
[0020]
The term "fragment" as used herein, is a polynucleotide having a nucleotide sequence of contiguous portion of a polynucleotide, 15 nucleotides or more, it is desirable that preferably 17 bases or more, more preferably having 19 or more bases in length .
The scope of the claims
[Claim 1]
食道 が ん マ ー カ ー で あ る, miR-204-3p, miR-1247-3p, miR-6875-5p, miR-6857-5p, miR-6726-5p, miR-3188, miR-8069, miR-4257, miR -1343-3p, miR-7108-5p, miR-6825-5p, miR-7641, miR-3185, miR-4746-3p, miR-6791-5p, miR-6893-5p, miR-4433b-3p, miR -3135b, miR-6781-5p, miR-1908-5p, miR-4792, miR-7845-5p, miR-4417, miR-3184-5p, miR-1225-5p, miR-1231, miR-1225-3p , miR-150-3p, miR-4433-3p, miR-6125, miR-4513, miR-6787-5p, miR-6784-5p, miR-615-5p, miR-6765-3p, miR-5572, miR -6842-5p, miR-8063, miR-6780b-5p, miR-187-5p, miR-128-1-5p, miR-6729-5p, miR-6741-5p, miR-6757-5p, miR-7110 -5p, miR-7975, miR-1233-5p, miR-6845-5p, miR-3937, miR-4467, miR-7109-5p, miR-6088, miR-6782-5p, miR-5195-3p, miR -4454, miR-6724-5p, miR-8072, miR-4516, miR-6756-5p, miR-4665-3p, miR-6826-5p, miR-6820-5p, miR-6887-5p, miR-3679 -5p, miR-7847-3p, miR-6721-5p, miR-3622a-5p, miR-939-5p, miR-602, miR-7977, miR-6749-5p, miR-1914-3p, miR-4651 , miR-4695-5p, miR-6848-5p, miR-1228-3p, miR-642b-3p, miR-6746-5p, miR-3620-5p, miR-3131, miR-6732-5p, miR-7113 3P, miR-23a-3p, miR-3154, miR-4723-5p, miR-3663-3p, miR-4734, miR-6816-5p, miR-4442, miR-4476, miR-423-5p, miR -1249, miR-6515-3p, miR-887-3p, miR-4741, miR-6766-3p, miR-4673, miR-6779-5p, miR-4706, miR-1268b, miR-4632-5p, miR -3197, miR-6798-5p, miR-711, miR-6840-3p, miR-6763-5p, miR-6727-5p, miR-371a-5p, miR-6824-5p, miR-4648, miR-1227 -5p, miR-564, miR-3679-3p, miR-2861, miR-6737-5p, miR-4725-3p, miR-6716-5p, miR-4675, miR-1915-3p, miR-671-5p , miR-3656, miR-6722-3p, miR-4707-5p, miR-4449, miR-1202, miR-4649-5p, miR-744-5p, miR-642a-3p, miR-451a, miR-6870 -5p, miR-4443, miR-6808-5p, miR-4728-5p, miR-937-5p, miR-135a-3p, miR-663b, miR-1343-5p, miR-6822-5p, miR-6803 -5p, miR-6805-3p, miR-128-2-5p, miR-4640-5p, miR-1469, miR-92a-2-5p, miR-3940-5p, miR-4281, miR-1260b, miR -4758-5p, miR-1915-5p, miR-5001-5p, miR-4286, miR-6126, miR-6789-5p, miR-4459, miR-1268a, miR-6752-5p, miR-6131, miR -6800-5p, miR-4532, miR-6872-3p, miR-718, miR-6769a-5p, miR-4707-3p, miR-6765-5p, miR-4739, miR-4525, miR-4270, miR -4534, miR-6785-5p, miR-6850-5p, miR-4697-5p, miR-1260a, miR-4486, miR-6880-5p, miR-6802-5p, miR-6861-5p, miR-92b -5p, miR-1238-5p, miR-6851-5p, miR-7704, miR-149-3p, miR-4689, miR-4688, miR-125a-3p, miR-23b-3p, miR-614, miR -1913, miR-16-5p, miR-6717-5p, miR-3648, miR-3162-5p, miR-1909-3p, miR-8073, miR-6769b-5p, miR-6836-3p, miR-4484 , miR-6819-5p 及 び miR-6794-5p か ら な る 群 か ら 選 択 さ れ る 少 な く と も 1 つ の ポ リ ヌ ク レ オ チ ド と 特異 的 に 結合 可能 な 核酸 を 含 む, 食道 が ん の 検 出 用 キ ッ ト.
[Claim 2]
miR-204-3p is hsa-miR-204-3p, miR- 1247-3p is hsa-miR-1247-3p, miR- 6875-5p is hsa-miR-6875-5p, miR- 6857-5p is hsa-miR-6857-5p, miR- 6726-5p is hsa-miR-6726-5p, miR- 3188 is hsa-miR-3188, miR- 8069 is hsa-miR- is 8069, miR-4257 is hsa-miR-4257, miR- 1343-3p is hsa-miR-1343-3p, miR- 7108-5p is hsa-miR-7108-5p, miR- 6825-5p is hsa-miR-6825-5p, miR- 7641 is hsa-miR-7641, miR- 3185 is hsa-miR-3185, miR- 4746-3p is hsa-miR-4746- is 3p, miR-6791-5p is hsa-miR-6791-5p, miR- 6893-5p is hsa-miR-6893-5p, miR- 4433b-3p is in hsa-miR-4433b-3p Yes, miR-3135b is hsa-miR-3135b, miR- 6781-5p is hsa-miR-6781-5p, miR- 1908-5p is hsa-miR-1908-5p, the miR-4792 is hsa-miR-4792, miR- 7845-5p is hsa-miR-7845-5p, miR- 4417 is hsa-miR-4417, miR- 3184-5p is in hsa-miR-3184-5p Yes, miR-1225-5p is hsa-miR-1225-5p, miR- 1231 is hsa-miR-1231, miR- 1225-3p is hsa-miR-1225-3p, miR- 150- 3p is hsa-miR-150-3p, miR- 4433-3p is hsa-miR-4433-3p, miR- 6125 is hsa-miR-6125, miR- 4513 is in the hsa-miR-4513 Yes, miR-6787-5p is hsa-miR-6787-5p, miR- 6784-5p is hsa-miR-6784-5p, miR- 615-5p is hsa-miR-615-5p, miR-6765-3p is hsa-miR-6765-3p, miR- 5572 is hsa-miR-5572, miR- 6842-5p is hsa-miR-6842-5p, miR- 8063 is hsa- is a miR-8063, miR-6780b- 5p is hsa-miR-6780b-5p, miR-187-5p is hsa-miR-187-5p, miR- 128-1-5p is hsa-miR- a 128-1-5p, miR-6729-5p is hsa-miR-6729-5p, miR- 6741-5p is hsa-miR-6741-5p, miR- 6757-5p is hsa-miR- a 6757-5p, miR-7110-5p is hsa-miR-7110-5p, miR- 7975 is hsa-miR-7975, miR- 1233-5p is hsa-miR-1233-5p, miR-6845-5p is hsa-miR-6845-5p, miR- 3937 is hsa-miR-3937, miR- 4467 is hsa-miR-4467, miR- 7109-5p is hsa-miR- a 7109-5p, miR-6088 is hsa-miR-6088, miR- 6782-5p is hsa-miR-6782-5p, miR- 5195-3p is hsa-miR-5195-3p, miR-4454 is hsa-miR-4454, miR- 6724-5p is hsa-miR-6724-5p, miR- 8072 is hsa-miR-8072, miR- 4516 is in the hsa-miR-4516 Yes, miR-6756-5p is hsa-miR-6756-5p, miR- 4665-3p is hsa-miR-4665-3p, miR- 6826-5p is hsa-miR-6826-5p, miR-6820-5p is hsa-miR-6820-5p, miR- 6887-5p is hsa-miR-6887-5p, miR- 3679-5p is hsa-miR-3679-5p, miR- 7847-3p is hsa-miR-7847-3p, miR- 6721-5p is hsa-miR-6721-5p, miR- 3622a-5p is hsa-miR-3622a-5p, miR-939- 5p is hsa-miR-939-5p, miR- 602 is hsa-miR-602, miR- 7977 is hsa-miR-7977, miR- 6749-5p is in hsa-miR-6749-5p Yes, miR-1914-3p is hsa-miR-1914-3p, miR- 4651 is hsa-miR-4651, miR- 4695-5p is hsa-miR-4695-5p, miR- 6848- 5p is hsa-miR-6848-5p, miR- 1228-3p is hsa-miR-1228-3p, miR- 642b-3p is hsa-miR-642b-3p, the miR-6746-5p is hsa-miR-6746-5p, miR- 3620-5p is hsa-miR-3620-5p, miR- 3131 is hsa-miR-3131, miR- 6732-5p is hsa-miR-6732- a 5p, miR-7113-3p is hsa-miR-7113-3p, miR- 23a-3p is hsa-miR-23a-3p, miR-3154 is hsa-miR-3154, miR- 4723-5p is hsa-miR-4723-5p, miR- 3663-3p is hsa-miR-3663-3p, miR- 4734 is hsa-miR-4734, is miR-6816-5p hsa- is a miR-6816-5p, miR-4442 is hsa-miR-4442, miR- 4476 is hsa-miR-4476, miR- 423-5p is hsa-miR-423-5p, miR- 1249 is hsa-miR-1249, miR- 6515-3p is hsa-miR-6515-3p, miR- 887-3p is hsa-miR-887-3p, miR- 4741 is hsa-miR- is 4741, miR-6766-3p is hsa-miR-6766-3p, miR- 4673 is hsa-miR-4673, miR- 6779-5p is hsa-miR-6779-5p, miR- 4706 is hsa-miR-4706, miR- 1268b is hsa-miR-1268b, miR- 4632-5p is hsa-miR-4632-5p, miR- 3197 is hsa-miR-3197, miR-6798-5p is hsa-miR-6798-5p, miR- 711 is hsa-miR-711, miR- 6840-3p is hsa-miR-6840-3p, the miR-6763-5p is hsa-miR-6763-5p, miR- 6727-5p is hsa-miR-6727-5p, miR- 371a-5p is hsa-miR-371a-5p, the miR-6824-5p hsa- is a miR-6824-5p, miR-4648 is hsa-miR-4648, miR- 1227-5p is hsa-miR-1227-5p, miR- 564 is hsa-miR-564, miR- 3679-3p is hsa-miR-3679-3p, miR- 2861 is hsa-miR-2861, miR- 6737-5p is hsa-miR-6737-5p, the miR-4725-3p hsa- is a miR-4725-3p, miR-6716-5p is hsa-miR-6716-5p, miR- 4675 is hsa-miR-4675, miR- 1915-3p is in hsa-miR-1915-3p Yes, miR-671-5p is hsa-miR-671-5p, miR- 3656 is hsa-miR-3656, miR- 6722-3p is hsa-miR-6722-3p, miR- 4707- 5p is hsa-miR-4707-5p, miR- 4449 is hsa-miR-4449, miR- 1202 is hsa-miR-1202, miR- 4649-5p is in hsa-miR-4649-5p Yes, miR-744-5p is hsa-miR-744-5p, miR- 642a-3p is hsa-miR-642a-3p, miR-451a is hsa-miR-451a, miR- 6870- 5p is hsa-miR-6870-5p, miR- 4443 is hsa-miR-4443, miR- 6808-5p is hsa-miR-6808-5p, miR- 4728-5p is hsa-miR- a 4728-5p, miR-937-5p is hsa-miR-937-5p, miR- 135a-3p is hsa-miR-135a-3p, miR-663b is hsa-miR-663b, miR-1343-5p is hsa-miR-1343-5p, miR- 6822-5p is hsa-miR-6822-5p, miR- 6803-5p is hsa-miR-6803-5p, miR- 6805-3p is hsa-miR-6805-3p, miR- 128-2-5p is hsa-miR-128-2-5p, miR- 4640-5p is hsa-miR-4640-5p, miR-1469 is hsa-miR-1469, miR- 92a-2-5p is hsa-miR-92a-2-5p, miR-3940-5p is hsa-miR-3940-5p, miR- 4281 is hsa-miR-4281, miR- 1260b is hsa-miR-1260b, miR- 4758-5p is hsa-miR-4758-5p, miR- 1915-5p is hsa-miR-1915- a 5p, miR-5001-5p is hsa-miR-5001-5p, miR- 4286 is hsa-miR-4286, miR- 6126 is hsa-miR-6126, is miR-6789-5p is hsa-miR-6789-5p, miR- 4459 is hsa-miR-4459, miR- 1268a is hsa-miR-1268a, miR- 6752-5p is hsa-miR-6752-5p, miR-6131 is hsa-miR-6131, miR- 6800-5p is hsa-miR-6800-5p, miR- 4532 is hsa-miR-4532, miR- 6872-3p is hsa-miR- a 6872-3p, miR-718 is hsa-miR-718, miR- 6769a-5p is hsa-miR-6769a-5p, miR-4707-3p is hsa-miR-4707-3p, miR-6765-5p is hsa-miR-6765-5p, miR- 4739 is hsa-miR-4739, miR- 4525 is hsa-miR-4525, miR- 4270 is in the hsa-miR-4270 Yes, miR-4534 is hsa-miR-4534, miR- 6785-5p is hsa-miR-6785-5p, miR- 6850-5p is hsa-miR-6850-5p, miR- 4697- 5p is hsa-miR-4697-5p, miR- 1260a is hsa-miR-1260a, miR- 4486 is hsa-miR-4486, miR- 6880-5p is in hsa-miR-6880-5p Yes, miR-6802-5p is hsa-miR-6802-5p, miR- 6861-5p is hsa-miR-6861-5p, miR- 92b-5p is hsa-miR-92b-5p,
123-miR 8-5P is hsa-miR-1238-5p, miR- 6851-5p is hsa-miR-6851-5p, miR- 7704 is hsa-miR-7704, miR- 149-3p there is a hsa-miR-149-3p, miR- 4689 is hsa-miR-4689, miR- 4688 there is hsa-miR-4688, miR- 125a-3p is hsa-miR-125a-3p, miR -23b-3p is hsa-miR-23b-3p, miR-614 is hsa-miR-614, miR- 1913 is hsa-miR-1913, miR- 16-5p is hsa-miR-16 a -5p, miR-6717-5p is hsa-miR-6717-5p, miR- 3648 is hsa-miR-3648, miR- 3162-5p is hsa-miR-3162-5p, miR -1909-3p is hsa-miR-1909-3p, miR- 8073 is hsa-miR-8073, miR- 6769b-5p is hsa-miR-6769b-5p, miR-6836-3p is hsa -miR-6836-3p is, miR-4484 is hsa-miR-4484, miR- 6819-5p is hsa-miR-6819-5p, and, miR-6794-5p is hsa-miR-6794 a -5p, kit of claim 1.
[Claim 3]
Said nucleic acid, the following (a) - shown in (e)
polynucleotides: (a) SEQ ID NO: 1 to 115 and 117 to 189, and, in the nucleotide sequence or the nucleotide sequence represented by any one of 666-675 u is a polynucleotide consisting of a nucleotide sequence which is t, a variant thereof, a fragment thereof comprising a derivative thereof, or 15 or more contiguous
bases, (b) SEQ ID NOs 115 and 117 to 189, and, 666 - 675 a polynucleotide comprising a nucleotide sequence represented by any
one, (c) SEQ ID NOs 115 and 117 to 189, and, u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 666-675 polynucleotides, a variant thereof comprising a nucleotide sequence complementary to the nucleotide sequence, the fragment comprising the derivative, or 15 or more contiguous
bases, (d-) SEQ ID NOs 115 and 117 to 189, and, 666-675 a polynucleotide comprising a complementary base sequence and the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of
the polynucleotide of any one of (e) above (a) ~ (d) and a polynucleotide hybridizing under stringent conditions,
a polynucleotide selected from the group consisting of a kit according to claim 1 or 2.
[Claim 4]
The kit further comprises a polynucleotide capable of specifically binding nucleic acids consisting of miR-575 and miR-24-3p, another esophageal cancer marker according to any one of claims 1 to 3 kit.
[Claim 5]
miR-575 is hsa-miR-575, miR-24-3p is hsa-miR-24-3p, kit according to claim 4.
[6.]
Said nucleic acid, a polynucleotide shown in the following (f) ~ (j):
(f) u In the nucleotide sequence or the nucleotide sequence represented by SEQ ID NO: 116 and 676 comprising the nucleotide sequence is t polynucleotide, its variants, derivatives thereof, or a fragment comprising 15 or more continuous
nucleotides, (g) a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 116 and
676, base represented by (h) SEQ ID NO: 116 and 676 a polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence u is t in sequence or the nucleotide sequence, the fragment comprising the variant, derivative, or 15 or more contiguous bases,
(i) SEQ ID NO: 116 and a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by 676, and
(j) any of the polynucleotides and string of said (f) ~ (i) a polynucleotide that hybridizes under stringent conditions,
a polynucleotide selected from the group consisting of a kit according to claim 4 or 5.
[7.]
The kit is another of esophageal cancer marker, miR-675-5p, miR-486-3p, miR-6777-5p, miR-4497, miR-296-3p, miR-6738-5p, miR-4731 -5p, miR-6889-5p, miR-6786-5p, miR-92a-3p, miR-4294, miR-4763-3p, miR-6076, miR-663a, miR-760, miR-4667-5p, miR -6090, miR-4730, miR-7106-5p, miR-3196, miR-5698, miR-6087, miR-4665-5p, at least one of which is selected from the group consisting of miR-8059 and miR-6879-5p further comprising a polynucleotide capable of specifically binding nucleic acids, the kit according to any one of claims 1 to 6.
[8.]
miR-675-5p is hsa-miR-675-5p, miR-486-3p is hsa-miR-486-3p, miR-6777-5p is hsa-miR-6777-5p, miR- 4497 is hsa-miR-4497, miR-296-3p is hsa-miR-296-3p, miR-6738-5p is hsa-miR-6738-5p, the miR-4731-5p hsa- is a miR-4731-5p, miR-6889-5p is hsa-miR-6889-5p, miR-6786-5p is hsa-miR-6786-5p, miR-92a-3p is hsa-miR- a 92a-3p, miR-4294 is hsa-miR-4294, miR-4763-3p is hsa-miR-4763-3p, miR-6076 is hsa-miR-6076, is miR-663a is hsa-miR-663a, miR-760 is hsa-miR-760, miR-4667-5p is hsa-miR-4667-5p, miR-6090 is hsa-miR-6090, miR- 4730 is hsa-miR-4730, miR-7106-5p is hsa-miR-7106-5p, miR-3196 is hsa-miR-3196, miR-5698 is hsa-miR-5698, miR-6087 is hsa-miR-6087, miR-4665-5p is hsa-miR-4665-5p, miR-8059 is hsa-miR-8059, and, the miR-6879-5p hsa- it is a miR-6879-5p, kit according to claim 7.
[9.]
It said nucleic acid, the following (k) a polynucleotide shown in ~ (o):
(k) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 190-214 are the nucleotide sequence is t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 190 to
214, (yd) SEQ ID NO: 190 to polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 214 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 190-214, and
(o) the (k) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (n),
is a polynucleotide selected from the group consisting of a kit according to claim 7 or 8.
[10.]
The kit comprises at least two nucleic respectively capable of specifically binding at least two polynucleotides selected from all esophageal cancer marker according to claim 1 or 2, any of claims 1 to 9 or kit according to item 1.
[11.]
食道 が ん マ ー カ ー で あ る, miR-204-3p, miR-1247-3p, miR-6875-5p, miR-6857-5p, miR-6726-5p, miR-3188, miR-8069, miR-4257, miR -1343-3p, miR-7108-5p, miR-6825-5p, miR-7641, miR-3185, miR-4746-3p, miR-6791-5p, miR-6893-5p, miR-4433b-3p, miR -3135b, miR-6781-5p, miR-1908-5p, miR-4792, miR-7845-5p, miR-4417, miR-3184-5p, miR-1225-5p, miR-1231, miR-1225-3p , miR-150-3p, miR-4433-3p, miR-6125, miR-4513, miR-6787-5p, miR-6784-5p, miR-615-5p, miR-6765-3p, miR-5572, miR -6842-5p, miR-8063, miR-6780b-5p, miR-187-5p, miR-128-1-5p, miR-6729-5p, miR-6741-5p, miR-6757-5p, miR-7110 -5p, miR-7975, miR-1233-5p, miR-6845-5p, miR-3937, miR-4467, miR-7109-5p, miR-6088, miR-6782-5p, miR-5195-3p, miR -4454, miR-6724-5p, miR-8072, miR-4516, miR-6756-5p, miR-4665-3p, miR-6826-5p, miR-6820-5p, miR-6887-5p, miR-3679 -5p, miR-7847-3p, miR-6721-5p, miR-3622a-5p, miR-939-5p, miR-602, miR-7977, miR-6749-5p, miR-1914-3p, miR-4651 , miR-4695-5p, miR-6848-5p, miR-1228-3p, miR-642b-3p, miR-6746-5p, miR-3620-5p, miR-3131, miR-6732-5p, miR-7113 3P, miR-23a-3p, miR-3154, miR-4723-5p, miR-3663-3p, miR-4734, miR-6816-5p, miR-4442, miR-4476, miR-423-5p, miR -1249, miR-6515-3p, miR-887-3p, miR-4741, miR-6766-3p, miR-4673, miR-6779-5p, miR-4706, miR-1268b, miR-4632-5p, miR -3197, miR-6798-5p, miR-711, miR-6840-3p, miR-6763-5p, miR-6727-5p, miR-371a-5p, miR-6824-5p, miR-4648, miR-1227 -5p, miR-564, miR-3679-3p, miR-2861, miR-6737-5p, miR-4725-3p, miR-6716-5p, miR-4675, miR-1915-3p, miR-671-5p , miR-3656, miR-6722-3p, miR-4707-5p, miR-4449, miR-1202, miR-4649-5p, miR-744-5p, miR-642a-3p, miR-451a, miR-6870 -5p, miR-4443, miR-6808-5p, miR-4728-5p, miR-937-5p, miR-135a-3p, miR-663b, miR-1343-5p, miR-6822-5p, miR-6803 -5p, miR-6805-3p, miR-128-2-5p, miR-4640-5p, miR-1469, miR-92a-2-5p, miR-3940-5p, miR-4281, miR-1260b, miR -4758-5p, miR-1915-5p, miR-5001-5p, miR-4286, miR-6126, miR-6789-5p, miR-4459, miR-1268a, miR-6752-5p, miR-6131, miR -6800-5p, miR-4532, miR-6872-3p, miR-718, miR-6769a-5p, miR-4707-3p, miR-6765-5p, miR-4739, miR-4525, miR-4270, miR -4534, miR-6785-5p, miR-6850-5p, miR-4697-5p, miR-1260a, miR-4486, miR-6880-5p, miR-6802-5p, miR-6861-5p, miR-92b -5p, miR-1238-5p, miR-6851-5p, miR-7704, miR-149-3p, miR-4689, miR-4688, miR-125a-3p, miR-23b-3p, miR-614, miR -1913, miR-16-5p, miR-6717-5p, miR-3648, miR-3162-5p, miR-1909-3p, miR-8073, miR-6769b-5p, miR-6836-3p, miR-4484 , miR-6819-5p 及 び miR-6794-5p か ら な る 群 か ら 選 択 さ れ る 少 な く と も 1 つ の ポ リ ヌ ク レ オ チ ド と 特異 的 に 結合 可能 な 核酸 を 含 む, 食道 が ん の 検 出 用 デ バ イ ス.
[12.]
miR-204-3p is hsa-miR-204-3p, miR- 1247-3p is hsa-miR-1247-3p, miR- 6875-5p is hsa-miR-6875-5p, miR- 6857-5p is hsa-miR-6857-5p, miR- 6726-5p is hsa-miR-6726-5p, miR- 3188 is hsa-miR-3188, miR- 8069 is hsa-miR- is 8069, miR-4257 is hsa-miR-4257, miR- 1343-3p is hsa-miR-1343-3p, miR- 7108-5p is hsa-miR-7108-5p, miR- 6825-5p is hsa-miR-6825-5p, miR- 7641 is hsa-miR-7641, miR- 3185 is hsa-miR-3185, miR- 4746-3p is hsa-miR-4746- is 3p, miR-6791-5p is hsa-miR-6791-5p, miR- 6893-5p is hsa-miR-6893-5p, miR- 4433b-3p is in hsa-miR-4433b-3p Yes, miR-3135b is hsa-miR-3135b, miR- 6781-5p is hsa-miR-6781-5p, miR- 1908-5p is hsa-miR-1908-5p, the miR-4792 is hsa-miR-4792, miR- 7845-5p is hsa-miR-7845-5p, miR- 4417 is hsa-miR-4417, miR- 3184-5p is in hsa-miR-3184-5p Yes, miR-1225-5p is hsa-miR-1225-5p, miR- 1231 is hsa-miR-1231, miR- 1225-3p is hsa-miR-1225-3p, miR- 150- 3p is hsa-miR-150-3p, miR- 4433-3p is hsa-miR-4433-3p, miR- 6125 is hsa-miR-6125, miR- 4513 is in the hsa-miR-4513 Yes, miR-6787-5p is hsa-miR-6787-5p, miR- 6784-5p is hsa-miR-6784-5p, miR- 615-5p is hsa-miR-615-5p, miR-6765-3p is hsa-miR-6765-3p, miR- 5572 is hsa-miR-5572, miR- 6842-5p is hsa-miR-6842-5p, miR- 8063 is hsa- is a miR-8063, miR-6780b- 5p is hsa-miR-6780b-5p, miR-187-5p is hsa-miR-187-5p, miR- 128-1-5p is hsa-miR- a 128-1-5p, miR-6729-5p is hsa-miR-6729-5p, miR- 6741-5p is hsa-miR-6741-5p, miR- 6757-5p is hsa-miR- a 6757-5p, miR-7110-5p is hsa-miR-7110-5p, miR- 7975 is hsa-miR-7975, miR- 1233-5p is hsa-miR-1233-5p, miR-6845-5p is hsa-miR-6845-5p, miR- 3937 is hsa-miR-3937, miR- 4467 is hsa-miR-4467, miR- 7109-5p is hsa-miR- a 7109-5p, miR-6088 is hsa-miR-6088, miR- 6782-5p is hsa-miR-6782-5p, miR- 5195-3p is hsa-miR-5195-3p, miR-4454 is hsa-miR-4454, miR- 6724-5p is hsa-miR-6724-5p, miR- 8072 is hsa-miR-8072, miR- 4516 is in the hsa-miR-4516 Yes, miR-6756-5p is hsa-miR-6756-5p, miR- 4665-3p is hsa-miR-4665-3p, miR- 6826-5p is hsa-miR-6826-5p, miR-6820-5p is hsa-miR-6820-5p, miR- 6887-5p is hsa-miR-6887-5p, miR- 3679-5p is hsa-miR-3679-5p, miR- 7847-3p is hsa-miR-7847-3p, miR- 6721-5p is hsa-miR-6721-5p, miR- 3622a-5p is hsa-miR-3622a-5p, miR-939- 5p is hsa-miR-939-5p, miR- 602 is hsa-miR-602, miR- 7977 is hsa-miR-7977, miR- 6749-5p is in hsa-miR-6749-5p Yes, miR-1914-3p is hsa-miR-1914-3p, miR- 4651 is hsa-miR-4651, miR- 4695-5p is hsa-miR-4695-5p, miR- 6848- 5p is hsa-miR-6848-5p, miR- 1228-3p is hsa-miR-1228-3p, miR- 642b-3p is hsa-miR-642b-3p, the miR-6746-5p is hsa-miR-6746-5p, miR- 3620-5p is hsa-miR-3620-5p, miR- 3131 is hsa-miR-3131, miR- 6732-5p is hsa-miR-6732- a 5p, miR-7113-3p is hsa-miR-7113-3p, miR- 23a-3p is hsa-miR-23a-3p, miR-3154 is hsa-miR-3154, miR- 4723-5p is hsa-miR-4723-5p, miR- 3663-3p is hsa-miR-3663-3p, miR- 4734 is hsa-miR-4734, is miR-6816-5p hsa- is a miR-6816-5p, miR-4442 is hsa-miR-4442, miR- 4476 is hsa-miR-4476, miR- 423-5p is hsa-miR-423-5p, miR- 1249 is hsa-miR-1249, miR- 6515-3p is hsa-miR-6515-3p, miR- 887-3p is hsa-miR-887-3p, miR- 4741 is hsa-miR- is 4741, miR-6766-3p is hsa-miR-6766-3p, miR- 4673 is hsa-miR-4673, miR- 6779-5p is hsa-miR-6779-5p, miR- 4706 is hsa-miR-4706, miR- 1268b is hsa-miR-1268b, miR- 4632-5p is hsa-miR-4632-5p, miR- 3197 is hsa-miR-3197, miR-6798-5p is hsa-miR-6798-5p, miR- 711 is hsa-miR-711, miR- 6840-3p is hsa-miR-6840-3p, the miR-6763-5p is hsa-miR-6763-5p, miR- 6727-5p is hsa-miR-6727-5p, miR- 371a-5p is hsa-miR-371a-5p, the miR-6824-5p hsa- is a miR-6824-5p, miR-4648 is hsa-miR-4648, miR- 1227-5p is hsa-miR-1227-5p, miR- 564 is hsa-miR-564, miR- 3679-3p is hsa-miR-3679-3p, miR- 2861 is hsa-miR-2861, miR- 6737-5p is hsa-miR-6737-5p, the miR-4725-3p hsa- is a miR-4725-3p, miR-6716-5p is hsa-miR-6716-5p, miR- 4675 is hsa-miR-4675, miR- 1915-3p is in hsa-miR-1915-3p Yes, miR-671-5p is hsa-miR-671-5p, miR- 3656 is hsa-miR-3656, miR- 6722-3p is hsa-miR-6722-3p, miR- 4707- 5p is hsa-miR-4707-5p, miR- 4449 is hsa-miR-4449, miR- 1202 is hsa-miR-1202, miR- 4649-5p is in hsa-miR-4649-5p Yes, miR-744-5p is hsa-miR-744-5p, miR- 642a-3p is hsa-miR-642a-3p, miR-451a is hsa-miR-451a, miR- 6870- 5p is hsa-miR-6870-5p, miR- 4443 is hsa-miR-4443, miR- 6808-5p is hsa-miR-6808-5p, miR- 4728-5p is hsa-miR- a 4728-5p, miR-937-5p is hsa-miR-937-5p, miR- 135a-3p is hsa-miR-135a-3p, miR-663b is hsa-miR-663b, miR-1343-5p is hsa-miR-1343-5p, miR- 6822-5p is hsa-miR-6822-5p, miR- 6803-5p is hsa-miR-6803-5p, miR- 6805-3p is hsa-miR-6805-3p, miR- 128-2-5p is hsa-miR-128-2-5p, miR- 4640-5p is hsa-miR-4640-5p, miR-1469 is hsa-miR-1469, miR- 92a-2-5p is hsa-miR-92a-2-5p, miR-3940-5p is hsa-miR-3940-5p, miR- 4281 is hsa-miR-4281, miR- 1260b is hsa-miR-1260b, miR- 4758-5p is hsa-miR-4758-5p, miR- 1915-5p is hsa-miR-1915- a 5p, miR-5001-5p is hsa-miR-5001-5p, miR- 4286 is hsa-miR-4286, miR- 6126 is hsa-miR-6126, is miR-6789-5p is hsa-miR-6789-5p, miR- 4459 is hsa-miR-4459, miR- 1268a is hsa-miR-1268a, miR- 6752-5p is hsa-miR-6752-5p, miR-6131 is hsa-miR-6131, miR- 6800-5p is hsa-miR-6800-5p, miR- 4532 is hsa-miR-4532, miR- 6872-3p is hsa-miR- a 6872-3p, miR-718 is hsa-miR-718, miR- 6769a-5p is hsa-miR-6769a-5p, miR-4707-3p is hsa-miR-4707-3p, miR-6765-5p is hsa-miR-6765-5p, miR- 4739 is hsa-miR-4739, miR- 4525 is hsa-miR-4525, miR- 4270 is in the hsa-miR-4270 Yes, miR-4534 is hsa-miR-4534, miR- 6785-5p is hsa-miR-6785-5p, miR- 6850-5p is hsa-miR-6850-5p, miR- 4697- 5p is hsa-miR-4697-5p, miR- 1260a is hsa-miR-1260a, miR- 4486 is hsa-miR-4486, miR- 6880-5p is in hsa-miR-6880-5p Yes, miR-6802-5p is hsa-miR-6802-5p, miR- 6861-5p is hsa-miR-6861-5p, miR- 92b-5p is hsa-miR-92b-5p,
123-miR 8-5P is hsa-miR-1238-5p, miR- 6851-5p is hsa-miR-6851-5p, miR- 7704 is hsa-miR-7704, miR- 149-3p There is a hsa-miR-149-3p, miR- 4689 is hsa-miR-4689, miR- 4688 is hsa-miR-4688, miR- 125a-3p is located in the hsa-miR-125a-3p , miR-23b-3p is hsa-miR-23b-3p, miR-614 is hsa-miR-614, miR- 1913 is hsa-miR-1913, miR- 16-5p is hsa-miR a -16-5p, miR-6717-5p is hsa-miR-6717-5p, miR- 3648 is hsa-miR-3648, miR- 3162-5p is located in the hsa-miR-3162-5p , miR-1909-3p is hsa-miR-1909-3p, miR- 8073 is hsa-miR-8073, miR- 6769b-5p is hsa-miR-6769b-5p, miR-6836-3p there is a hsa-miR-6836-3p, miR- 4484 is hsa-miR-4484, miR- 6819-5p is hsa-miR-6819-5p, and, miR-6794-5p is hsa-miR a -6794-5p, the device according to claim 11.
[13.]
Said nucleic acid, the following (a) - shown in (e)
polynucleotides: (a) SEQ ID NO: 1 to 115 and 117 to 189, and, in the nucleotide sequence or the nucleotide sequence represented by any one of 666-675 u is a polynucleotide consisting of a nucleotide sequence which is t, a variant thereof, a fragment thereof comprising a derivative thereof, or 15 or more contiguous
bases, (b) SEQ ID NOs 115 and 117 to 189, and, 666 - 675 a polynucleotide comprising a nucleotide sequence represented by any
one, (c) SEQ ID NOs 115 and 117 to 189, and, u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 666-675 polynucleotides, a variant thereof comprising a nucleotide sequence complementary to the nucleotide sequence, the fragment comprising the derivative, or 15 or more contiguous
bases, (d-) SEQ ID NOs 115 and 117 to 189, and, 666-675 a polynucleotide comprising a complementary base sequence and the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of
the polynucleotide of any one of (e) above (a) ~ (d) and a polynucleotide hybridizing under stringent conditions,
a polynucleotide selected from the group consisting of claim 11 or 12 devices.
[14.]
It said device is another esophageal cancer marker, further comprising a polynucleotide capable of specifically binding nucleic acids consisting of miR-575 and miR-24-3p, according to any one of claims 11 to 13 of the device.
[15.]
miR-575 is hsa-miR-575, miR-24-3p is hsa-miR-24-3p, device according to claim 14.
[16.]
Said nucleic acid, a polynucleotide shown in the following (f) ~ (j):
(f) u In the nucleotide sequence or the nucleotide sequence represented by SEQ ID NO: 116 and 676 comprising the nucleotide sequence is t polynucleotide, its variants, derivatives thereof, or a fragment comprising 15 or more continuous
nucleotides, (g) a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 116 and
676, base represented by (h) SEQ ID NO: 116 and 676 a polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence u is t in sequence or the nucleotide sequence, the fragment comprising the variant, derivative, or 15 or more contiguous bases,
(i) SEQ ID NO: 116 and a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by 676, and
(j) any of the polynucleotides and string of said (f) ~ (i) a polynucleotide that hybridizes under stringent conditions,
a polynucleotide selected from the group consisting of a device according to claim 14 or 15.
[17.]
The device is another of esophageal cancer marker, miR-675-5p, miR-486-3p, miR-6777-5p, miR-4497, miR-296-3p, miR-6738-5p, miR-4731 -5p, miR-6889-5p, miR-6786-5p, miR-92a-3p, miR-4294, miR-4763-3p, miR-6076, miR-663a, miR-760, miR-4667-5p, miR -6090, miR-4730, miR-7106-5p, miR-3196, miR-5698, miR-6087, miR-4665-5p, at least one of which is selected from the group consisting of miR-8059 and miR-6879-5p further comprising a polynucleotide capable of specifically binding nucleic acids, a device according to any one of claims 11 to 16.
[18.]
miR-675-5p is hsa-miR-675-5p, miR-486-3p is hsa-miR-486-3p, miR-6777-5p is hsa-miR-6777-5p, miR- 4497 is hsa-miR-4497, miR-296-3p is hsa-miR-296-3p, miR-6738-5p is hsa-miR-6738-5p, the miR-4731-5p hsa- is a miR-4731-5p, miR-6889-5p is hsa-miR-6889-5p, miR-6786-5p is hsa-miR-6786-5p, miR-92a-3p is hsa-miR- a 92a-3p, miR-4294 is hsa-miR-4294, miR-4763-3p is hsa-miR-4763-3p, miR-6076 is hsa-miR-6076, is miR-663a is hsa-miR-663a, miR-760 is hsa-miR-760, miR-4667-5p is hsa-miR-4667-5p, miR-6090 is hsa-miR-6090, miR- 4730 is hsa-miR-4730, miR-7106-5p is hsa-miR-7106-5p, miR-3196 is hsa-miR-3196, miR-5698 is hsa-miR-5698, miR-6087 is hsa-miR-6087, miR-4665-5p is hsa-miR-4665-5p, miR-8059 is hsa-miR-8059, and, the miR-6879-5p hsa- it is a miR-6879-5p, device of claim 17.
[19.]
It said nucleic acid, the following (k) a polynucleotide shown in ~ (o):
(k) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 190-214 are the nucleotide sequence is t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 190 to
214, (yd) SEQ ID NO: 190 to polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 214 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 190-214, and
(o) the (k) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (n),
is a polynucleotide selected from the group consisting of, a device according to claim 17 or 18.
[20.]
It said device is a device for measuring by hybridization techniques, according to any one of claims 11 to 19 devices.
[21.]
The hybridization techniques, a nucleic acid array technology, according to claim 20 devices.
[22.]
The device comprises at least two nucleic respectively capable of specifically binding at least two polynucleotides selected from all esophageal cancer marker according to claim 11 or 12, any of claims 11-21 device according to item 1 or.
[23.]
Using a device according to any one of claims 1 kit according to any one of 10 or claims 11 to 22 to measure the expression level of a target nucleic acid in the specimen of a subject, is the measurement and the expression level, as well as the subject using the control expression level of the measured healthy body is suffering from esophageal cancer, or be assessed in vitro a not to be suffering from esophageal cancer including a method for detecting esophageal cancer.
[24.]
The subject is a human The method of claim 23.
[25.]
The sample is blood, serum or plasma Method according to claim 23 or 24.
| # | Name | Date |
|---|---|---|
| 1 | Sequence listing(PDF) [16-01-2017(online)].pdf | 2017-01-16 |
| 2 | Sequence listing [16-01-2017(online)].txt | 2017-01-16 |
| 4 | PROOF OF RIGHT [16-01-2017(online)].pdf | 2017-01-16 |
| 5 | Power of Attorney [16-01-2017(online)].pdf | 2017-01-16 |
| 6 | Form 5 [16-01-2017(online)].pdf | 2017-01-16 |
| 7 | Form 3 [16-01-2017(online)].pdf | 2017-01-16 |
| 8 | Drawing [16-01-2017(online)].pdf | 2017-01-16 |
| 9 | Description(Complete) [16-01-2017(online)].pdf_10.pdf | 2017-01-16 |
| 10 | Description(Complete) [16-01-2017(online)].pdf | 2017-01-16 |
| 11 | Other Document [30-03-2017(online)].pdf | 2017-03-30 |
| 12 | Marked Copy [30-03-2017(online)].pdf | 2017-03-30 |
| 13 | Form 13 [30-03-2017(online)].pdf | 2017-03-30 |
| 14 | Description(Complete) [30-03-2017(online)].pdf_273.pdf | 2017-03-30 |
| 15 | Description(Complete) [30-03-2017(online)].pdf | 2017-03-30 |
| 16 | Information under section 8(2) [01-07-2017(online)].pdf | 2017-07-01 |
| 17 | 201737001669-FORM-26 [05-02-2018(online)].pdf | 2018-02-05 |
| 18 | 201737001669-MARKED COPIES OF AMENDEMENTS [15-06-2018(online)].pdf | 2018-06-15 |
| 19 | 201737001669-FORM 18 [15-06-2018(online)].pdf | 2018-06-15 |
| 20 | 201737001669-AMMENDED DOCUMENTS [15-06-2018(online)].pdf | 2018-06-15 |
| 21 | 201737001669-Amendment Of Application Before Grant - Form 13 [15-06-2018(online)].pdf | 2018-06-15 |
| 22 | 201737001669-FORM 3 [18-04-2020(online)].pdf | 2020-04-18 |
| 23 | 201737001669-FER.pdf | 2020-08-11 |
| 24 | 201737001669-AbandonedLetter.pdf | 2024-07-12 |
| 1 | 2020-08-1016-22-32E_10-08-2020.pdf |