Pancreatic cancer detection kit or device and detection method

Abstract

To discover novel pancreatic cancer tumor markers, and to provide methods for effectively detecting pancreatic cancer using a nucleic acid that can specifically bind to the marker.SOLUTION: Provided are a pancreatic cancer detection kit or device comprising a nucleic acid capable of specifically binding to the miRNA in a subject's sample, and a method for detecting pancreatic cancer comprising measuring the miRNA in vitro.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present invention relates to a specific method for detecting the presence or absence of pancreatic cancer in a subject. A kit or device for detecting pancreatic cancer, comprising a nucleic acid capable of specifically binding to miRNA, and and a method for detecting pancreatic cancer, which comprises measuring the expression level of the miRNA using the nucleic acid. do. [Background technology]

[0002] The pancreas is an exocrine gland that secretes pancreatic juice, a digestive fluid, and sends it to the digestive tract through the pancreatic duct. It also functions as an endocrine gland that secretes hormones such as insulin and glucagon into the blood. It also has

[0003] The pancreas is surrounded by many organs, including the stomach, duodenum, small intestine, liver, and gallbladder, so early detection of cancer is possible. Not only is it difficult to detect, it is asymptomatic, progresses very quickly, and metastasizes to other organs. It has properties such as stinging and has an extremely poor prognosis compared to other cancers. 2011, published by the National Cancer Center, Cancer Control and Information Center (Tokyo, Japan) According to statistics on cancer mortality rates by site in Japan in 2015, the number of deaths from pancreatic cancer was 28.8%. The number of patients with pancreatic cancer was 29, and the 5-year relative survival rate by site from 2003 to 2005 was the lowest. The rate is 7.1% for men and 6.9% for women.

[0004] As described in Non-Patent Document 1, the basic treatment for pancreatic cancer is surgery, total resection, or rectal resection depending on the stage of progression. It is performed with chemotherapy, radiation therapy, or a combination of these. 15-20% of pancreatic cancer patients Although surgery is considered a cure for some patients, most patients who did not undergo surgery have local The median survival time was 1.5 years for locally advanced cancer. It is said that the survival time for cancer is 8 to 12 months for normal cancer and 3 to 6 months for metastatic cancer, which is very long compared to other cancers. .

[0005] UICC(Unio Internationalis Contra Cancru) The progression of pancreatic cancer according to the 5th edition of the Guidelines for the Treatment of Pancreatic Cancer (edited by the Japan Pancreas Society, published by Kanehara Publishing Co., Ltd.) The criteria are as follows: local extent of tumor, lymph node metastasis, distant metastasis, etc. Depending on the stage, it can be divided into stages 0, IA, IB, IIA, IIB, III, IVa, and IVb. Stage I-III accounts for more than half of the 5-year survival cases, and The progression rate is Stage IVa and Stage IVb, accounting for more than 70% of cases. Symptoms vary depending on the location of the cancer. In the case of pancreatic head cancer, symptoms may include jaundice. However, pancreatic tail cancer rarely causes symptoms. tends to be diagnosed late.

[0006] As described in Non-Patent Document 2, abdominal ultrasound is a simple and convenient method for diagnosing pancreatic cancer. This is a minimally invasive test that is extremely useful in outpatient care and screening. Small pancreatic cancers and lesions in the tail of the pancreas are often difficult to visualize. The rate of findings in pancreatic ultrasound images is approximately 1%, and the rate of pancreatic cancer detection is low at approximately 0.06% or less. In addition, tumor markers for detecting pancreatic cancer include, for example, the carbohydrate antigen CA19-9. , Span-1, CA50, CA242, Dupan-2, TAG-72, urinary fucose Other known antigens besides sugar chains include CEA, POA, and TPS. The marker is used when the blood concentration is higher or lower than a predetermined reference value. For example, as described in Non-Patent Document 3, the standard value of CEA is 5 The standard value for CA19-9 is set at 37U / mL, and values above this are In cases where the tumor marker level is high, cancer, including pancreatic cancer, is suspected. This is a study of advanced pancreatic cancer, and early-stage pancreatic cancer often does not show abnormal values. Even with tumor marker and abdominal ultrasound screening, the detection rate for pancreatic cancer is low. The implementation of these screening tests for this condition is problematic in terms of cost-effectiveness.

[0007] Although it is still in the research stage, as shown in Patent Documents 1 to 4, it is possible to detect biological samples such as blood. The expression level of microRNA (miRNA) in the pool, or the expression level of miRNA and other proteins There are reports that pancreatic cancer can be identified by combining the expression levels of protein markers. be.

[0008] Patent Document 1 describes how hsa-miR-125a-3p in blood is regulated by several dozen other miRNAs. A method for detecting pancreatic cancer in combination with

[0009] Patent Document 2 describes the precursor of hsa-miR-204-3p, hsa-m The precursor of iR-423-5p or the precursor of hsa-miR-328-5p, along with hundreds of other A method for detecting pancreatic cancer in combination with miRNAs has been demonstrated.

[0010] Patent Document 3 describes the detection of hsa-miR-575, hsa-miR-16-5p, or Combines hsa-miR-24-3p with hundreds of other miRNAs to detect pancreatic cancer It shows how to do this.

[0011] Patent Document 4 describes how hsa-miR-451a in blood and tissues is regulated by several dozen other miRNAs. A method for detecting pancreatic cancer in combination with

[0012] Patent Document 5 describes a precursor or hsa-miR-150-3p in blood or tissues. Precursor of miR-187-5p combined with hundreds of other miRNAs to detect pancreatic cancer It shows how to do this.

[0013] Non-patent document 4 reports on the effects of hsa-miR-423-5p and hsa-miR-124 in plasma. 6, hsa-miR-150-3p, hsa-miR-550a-5p, hsa-miR -371a-5p, hsa-miR-1469, hsa-miR-575, hsa-mi R-564, hsa-miR-125a-3p, hsa-miR-451a, hsa-m iR-1908-5p and other miRNs are expressed at significantly different levels between pancreatic cancer patients and healthy individuals. It is shown as A.

[0014] Non-patent document 5 reports that plasma miR-3188, miR-16-5p, etc. are involved in pancreatic cancer. It is shown as a miRNA whose expression level is significantly different between patients and healthy subjects.

[0015] Non-patent document 6 reports on serum miR-550a-5p, miR-1290, and miR-2 4-3p, miR-486-3p, miR-423-5p, miR-125a-3p, etc. has been shown to be a miRNA whose expression level is significantly different between pancreatic cancer patients and healthy individuals.

[0016] Non-patent document 7 states that the expression level of miR-602 in tissues is significantly different between pancreatic cancer patients and healthy individuals. are shown as differentially expressed miRNAs. [Prior art documents] [Patent documents]

[0017] [Patent Document 1] Special Publication 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 [Patent Document 5] US Patent Application Publication No. 2008 / 0306018 [Non-patent literature]

[0018] [Non-Patent Document 1] Tetsuya Mine, "Pancreas", Japan Pancreas Society, 2007, Vol. 22, pp. 10-13 [Non-patent document 2] Japan Pancreas Society "Evidence-Based Guidelines for the Management of Pancreatic Cancer 2009 Edition" CQ1 Diagnostic Method http: / / www.suizou.org / PCMG2009 / cq1 / cq1-3.html [Non-patent document 3] Kiyoshi Kurokawa et al., Clinical Laboratory Data Book, 2013, pp. 633, 636 (Igaku Shoin, Tokyo, Japan) [Non-patent document 4] Ali S. et al., 2011, American Journal of Translational Research, Vol. 3, (1) p28-47 [Non-Patent Document 5] Ganepola GA. et al., 2014, World Journal of Gastrointestinal Oncology. Vol. 6, (1) p22-33 [Non-patent document 6] Li A. et al., 2013, Clinical Cancer Ressearch, Vol. 19, (13), p3600-3610 [Non-Patent Document 7] Zhang J. et al., 2014, Oncology Reports, Vol. 31, (3), p1157-1164 Summary of the Invention [Problem to be solved by the invention]

[0019] The object of the present invention is to discover a novel pancreatic cancer tumor marker and to develop a method for producing a tumor marker that specifically binds to the marker. The object of the present invention is to provide a method for effectively detecting pancreatic cancer using nucleic acids that can be used. As described in Reference 2, tumor markers for detecting pancreatic cancer include, for example, carbohydrate antigens and CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-7 2. Urinary fucose, or antigens other than sugar chains such as CEA, POA, and TPS are known. The sensitivity of these tumor markers for detecting pancreatic cancer is 70-80% for CA19-9. , Span-1 70-80%, Dupan-2 50-60%, CEA 30-60% , CA50 is 60%, and the specificity is not so high, with a high false positive rate of 20-30%. Other cancers and / or benign tumors and / or diseases of the pancreas and / or surrounding organs In addition, the detection sensitivity of early-stage pancreatic cancer is generally The CA19-9 positive rate is only 52% for pancreatic cancers less than 2 cm in size, so It is not useful for detecting early-stage pancreatic cancer. In cases of blood type negative, the antigen is not produced and false negatives are observed, making this test unsuitable for some subjects. be.

[0020] Although still in the research stage, microRNAs (miR) in biological samples such as blood There are reports on the use of the expression level of NA to distinguish pancreatic cancer, as shown below. It has not yet been put into practical use.

[0021] In Patent Document 1, hsa-miR-125a-3p in the blood is isolated from dozens of other miRs. Methods for diagnosing various cancers, including pancreatic cancer, in combination with iRNA have been described. There is no description of its detection performance, such as specific accuracy, sensitivity, and specificity, and There is also no description of a method for diagnosing pancreatic cancer.

[0022] In Patent Document 2, the precursor of hsa-miR-204-3p in blood and tissues, hsa-m The precursor of iR-423-5p or the precursor of hsa-miR-328-5p, along with hundreds of other A method for detecting pancreatic cancer in combination with miRNA has been described, but its specific There is no description of the detection performance such as accuracy, sensitivity, specificity, etc., and the specific pancreas using blood The method for diagnosing the disease is not described.

[0023] In the method described in Patent Document 3, hsa-miR-575, hsa-miR-16-5p or hsa-miR-24-3p in combination with hundreds of other miRNAs to target pancreatic cancer There is no description that a diagnosis can be made by combining several miRNAs.

[0024] In Patent Document 4, hsa-miR-451a in pancreatic cancer tissue was detected by combining several dozen or more other miRs. RNA is used in combination to diagnose pancreatic cancer, but specific pancreatic cancers using blood The diagnostic method has not been described.

[0025] In Patent Document 5, a precursor of hsa-miR-150-3p or hsa in pancreatic cancer tissue is -The precursor of miR-187-5p was combined with hundreds of other miRNAs to treat pancreatic cancer. However, there are no reports on its detection performance, such as specific accuracy, sensitivity, and specificity. There is no mention of a specific method for diagnosing pancreatic cancer using blood.

[0026] In Non-Patent Document 4, miRNAs with significant differences in expression levels between the plasma of pancreatic cancer patients and healthy individuals are As examples, miR-423-5p, miR-1246, miR-150-3p, miR- 550a-5p, miR-371a-5p, miR-1469, miR-575, miR -564, miR-125a-3p, miR-451a, miR-1908-5p, etc. However, there is no description of their detection performance such as specific accuracy, sensitivity, specificity, etc. stomach.

[0027] In Non-Patent Document 5, miRNAs with significantly different expression levels in the plasma of pancreatic cancer patients and healthy individuals were miR-3188, miR-16-5p, etc. have been cited as examples of these factors, but verification has revealed that It was excluded from the analysis due to its low reliability.

[0028] In Non-Patent Document 6, miRNAs with significant differences in expression levels in the serum of pancreatic cancer patients and healthy individuals are as miR-550a-5p, miR-1290, miR-24-3p, and miR-4 86-3p, miR-423-5p, miR-125a-3p, etc. miR-550a-5p, miR-24-3p, miR-486-3p, miR-423 Regarding the detection performance of miR-5p and miR-125a-3p, such as specific accuracy, sensitivity, and specificity, There is no description of the detection performance of miR-1290, and the detection performance of miR-1290 has not been verified in an independent group of samples.

[0029] In Non-Patent Document 7, miRs with significant differences in expression levels between pancreatic tissues of pancreatic cancer patients and healthy individuals were miR-602 has been cited as an NA, but its specific accuracy, sensitivity, specificity, etc. There is no description of the detection performance, and no specific method for diagnosing pancreatic cancer using blood. It has not been done.

[0030] Thus, existing tumor markers have poor performance or are ineffective in detecting pancreatic cancer. The performance and detection methods of research-stage markers have not been specifically described, so these When using this method, unnecessary additional testing can be avoided by misidentifying healthy subjects as pancreatic cancer patients. There is a possibility that treatment opportunities may be missed due to overlooking the treatment or overlooking pancreatic cancer patients. Measuring miRNAs consisting of tens to hundreds of miRNAs increases the cost of testing, so It is difficult to use for large-scale screening such as breast cancer screening. Since collecting pancreatic tissue for this purpose is highly invasive to patients and undesirable, we are trying to collect it in a minimally invasive manner. It can be detected from blood samples taken, and pancreatic cancer patients can be compared with healthy subjects. There is a need for a highly accurate pancreatic cancer marker that can accurately distinguish pancreatic cancer. Since surgical resection is the only curative treatment, highly sensitive pancreatic cancer markers are desperately needed. . [Means for solving the problem]

[0031] As a result of intensive research aimed at solving the above problems, the present inventors have discovered a method for extracting pancreatic tissue from blood, which can be collected minimally invasively. We have identified several genes that can be used as cancer detection markers, and have identified nucleic acids that can specifically bind to these genes. By using the above method, it was found that pancreatic cancer can be significantly detected, and the present invention was completed. I arrived.

[0032] <Summary of the Invention> That is, the present invention has the following features.

[0033] (1) Pancreatic cancer markers: miR-6893-5p, miR-6075, and miR- 6820-5p, miR-4294, miR-6729-5p, miR-4476, mi R-6836-3p, miR-6765-3p, miR-6799-5p, miR-45 30, miR-7641, miR-4454, miR-615-5p, miR-8073 , miR-663a, miR-4634, miR-4450, miR-4792, miR -665, miR-7975, miR-7109-5p, miR-6789-5p, mi R-4497, miR-6877-5p, miR-6880-5p, miR-7977, miR-4734, miR-6821-5p, miR-8089, miR-5585-3 p, miR-6085, miR-6845-5p, 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, mi R-6872-3p, miR-6875-5p, miR-1908-3p, miR-44 33b-3p, miR-4736, miR-5100, miR-6724-5p, miR -7107-5p, miR-6726-5p, miR-3185, miR-4638-5 p, miR-1273g-3p, miR-6778-5p, miR-328-5p, mi R-3679-3p, miR-1228-3p, miR-6779-5p, miR-47 23-5p, miR-6850-5p, miR-760, miR-7704, miR-8 072, miR-4486, miR-1913, miR-4656, miR-1260b , miR-7106-5p, miR-6889-5p, miR-6780b-5p, mi R-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- 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, m iR-940, miR-4327, miR-4665-3p, miR-718, miR- 1203, miR-663b, miR-4258, miR-4649-5p, miR-4 516, miR-3619-3p, miR-6826-5p, miR-6757-5p, miR-3131, miR-1343-3p, miR-6775-5p, miR-681 At least one selected from the group consisting of miR-3-5p and miR-3940-5p A kit for detecting pancreatic cancer, comprising a nucleic acid capable of specifically binding to a polynucleotide of the present invention.

[0034] (2) miR-6893-5p is hsa-miR-6893-5p and miR-60 75 is hsa-miR-6075, and miR-6820-5p is hsa-miR-6 820-5p, miR-4294 is hsa-miR-4294, and miR-6 729-5p is hsa-miR-6729-5p, and miR-4476 is hsa-m iR-4476 and miR-6836-3p is hsa-miR-6836-3p miR-6765-3p is hsa-miR-6765-3p, and miR-679 9-5p is hsa-miR-6799-5p, and miR-4530 is hsa-miR -4530, miR-7641 is hsa-miR-7641, and miR-44 54 is hsa-miR-4454, and miR-615-5p is hsa-miR-61 5-5p, miR-8073 is hsa-miR-8073, and miR-663 a is hsa-miR-663a and miR-4634 is hsa-miR-4634 miR-4450 is hsa-miR-4450 and miR-4792 is hsa -miR-4792, miR-665 is hsa-miR-665, and miR- 7975 is hsa-miR-7975 and miR-7109-5p is hsa-miR -7109-5p, and miR-6789-5p is hsa-miR-6789-5p miR-4497 is hsa-miR-4497, and miR-6877-5p is hsa-miR-6877-5p and miR-6880-5p are hsa-miR-6 880-5p, miR-7977 is hsa-miR-7977, and miR-4 734 is hsa-miR-4734, and miR-6821-5p is hsa-miR- 6821-5p, miR-8089 is hsa-miR-8089, and miR- 5585-3p is hsa-miR-5585-3p, and miR-6085 is hsa- miR-6085 and miR-6845-5p are hsa-miR-6845-5p. miR-4651 is hsa-miR-4651, and miR-4433-3p is hsa-miR-4433-3p and miR-1231 , miR-4665-5p is hsa-miR-4665-5p, and miR-7 114-5p is hsa-miR-7114-5p, and miR-1238-5p is hs a-miR-1238-5p and miR-8069 is hsa-miR-8069 miR-4732-5p is hsa-miR-4732-5p, and miR-619 -5p is hsa-miR-619-5p, and miR-3622a-5p is hsa-m iR-3622a-5p and miR-1260a is hsa-miR-1260a miR-6741-5p is hsa-miR-6741-5p, and miR-678 1-5p is hsa-miR-6781-5p, and miR-6125 is hsa-miR -6125, and miR-6805-5p is hsa-miR-6805-5p, miR-6132 is hsa-miR-6132 and miR-6872-3p is hsa -miR-6872-3p and miR-6875-5p are hsa-miR-6875 -5p, miR-1908-3p is hsa-miR-1908-3p, and mi R-4433b-3p is hsa-miR-4433b-3p, and miR-4736 is hsa-miR-4736 and miR-5100 are hsa-miR-5100 , miR-6724-5p is hsa-miR-6724-5p, and miR-7107 -5p is hsa-miR-7107-5p, and miR-6726-5p is hsa-m iR-6726-5p, miR-3185 is hsa-miR-3185, and m iR-4638-5p is hsa-miR-4638-5p, and miR-1273g- 3p is hsa-miR-1273g-3p, and miR-6778-5p is hsa-m iR-6778-5p and miR-328-5p are hsa-miR-328-5p. miR-3679-3p is hsa-miR-3679-3p, and miR-12 28-3p is hsa-miR-1228-3p, and miR-6779-5p is hsa -miR-6779-5p, and miR-4723-5p is hsa-miR-4723 -5p, miR-6850-5p is hsa-miR-6850-5p, and mi R-760 is hsa-miR-760, and miR-7704 is hsa-miR-77 04, miR-8072 is hsa-miR-8072, and miR-4486 is hsa-miR-4486 and miR-1913 are hsa-miR-1913 , miR-4656 is hsa-miR-4656, and miR-1260b is hsa- miR-1260b and miR-7106-5p are hsa-miR-7106-5p , miR-6889-5p is hsa-miR-6889-5p, and miR-6 780b-5p is hsa-miR-6780b-5p, and miR-6090 is hsa -miR-6090, miR-4534 is hsa-miR-4534, mi R-4449 is hsa-miR-4449, and miR-5195-3p is hsa-m iR-5195-3p, miR-1202 is hsa-miR-1202, and m iR-4467 is hsa-miR-4467, and miR-6515-3p is hsa- miR-6515-3p, miR-4281 is hsa-miR-4281, miR-4505 is hsa-miR-4505 and miR-4484 is hsa-mi R-4484, and miR-6805-3p is hsa-miR-6805-3p , miR-3135b is hsa-miR-3135b, and miR-3162-5p is hsa-miR-3162-5p and miR-6768-5p are hsa-miR-6 768-5p, miR-6721-5p is hsa-miR-6721-5p , miR-1227-5p is hsa-miR-1227-5p, and miR-6722 -3p is hsa-miR-6722-3p, and miR-4286 is hsa-miR- 4286, miR-4746-3p is hsa-miR-4746-3p, and m iR-6727-5p is hsa-miR-6727-5p and miR-6816-5 p is hsa-miR-6816-5p and miR-4741 is hsa-miR-47 41, miR-4508 is hsa-miR-4508, and miR-940 is h sa-miR-940, miR-4327 is hsa-miR-4327, and m iR-4665-3p is hsa-miR-4665-3p, and miR-718 is hs a-miR-718, miR-1203 is hsa-miR-1203, and mi R-663b is hsa-miR-663b, and miR-4258 is hsa-miR- 4258, miR-4649-5p is hsa-miR-4649-5p, and m iR-4516 is hsa-miR-4516, and miR-3619-3p is hsa- miR-3619-3p and miR-6826-5p are hsa-miR-6826- 5p, miR-6757-5p is hsa-miR-6757-5p, and miR -3131 is hsa-miR-3131, and miR-1343-3p is hsa-mi miR-1343-3p and miR-6775-5p are hsa-miR-6775-5p and miR-6813-5p is hsa-miR-6813-5p, and mi The kit according to (1), wherein R-3940-5p is hsa-miR-3940-5p.

[0035] (3) The nucleic acid is a polynucleotide represented by any one of the following (a) to (e): (a) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A polynucleotide consisting of a base sequence or a base sequence in which u is t , a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (b) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 a polynucleotide comprising a base sequence; (c) Represented by any of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A base sequence that is complementary to a base sequence in which u is replaced by t. a polynucleotide containing 15 or more consecutive bases, a variant thereof, a derivative thereof, or a sequence thereof containing 15 or more consecutive bases piece, (d) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 Contains a base sequence or a base sequence complementary to the base sequence in which u is replaced by t polynucleotides, and (e) A polynucleotide that binds to any one of the polynucleotides (a) to (d) under stringent conditions. hybridizing polynucleotides, The kit according to (1) or (2), wherein the polynucleotide is selected from the group consisting of:

[0036] (4) The nucleic acid contains miR-125a-3p, miR-204-3p, or miR-1469 , miR-575, miR-150-3p, miR-423-5p, miR-564, m iR-3188, miR-1246, miR-602, miR-1290, miR-16 -5p, miR-451a, miR-24-3p, miR-187-5p, miR-19 miR-08-5p, miR-371a-5p, and miR-550a-5p. (The nucleic acid further comprises a nucleic acid capable of specifically binding to at least one or more polynucleotides selected from the group consisting of: The kit according to any one of 1) to (3).

[0037] (5) miR-125a-3p is hsa-miR-125a-3p, and miR-20 4-3p is hsa-miR-204-3p, and miR-1469 is hsa-miR- 1469, miR-575 is hsa-miR-575, and miR-150-3 p is hsa-miR-150-3p and miR-423-5p is hsa-miR-4 23-5p, miR-564 is hsa-miR-564, and miR-3188 is hsa-miR-3188 and miR-1246 is hsa-miR-1246 miR-602 is hsa-miR-602, and miR-1290 is hsa-mi R-1290, miR-16-5p is hsa-miR-16-5p, and miR -451a is hsa-miR-451a, and miR-24-3p is hsa-miR- 24-3p, miR-187-5p is hsa-miR-187-5p, and mi R-1908-5p is hsa-miR-1908-5p, and miR-371a-5p is hsa-miR-371a-5p, and miR-550a-5p is hsa-m The kit according to (4), wherein the kit is iR-550a-5p.

[0038] (6) The nucleic acid is a polynucleotide represented by any one of the following (f) to (j): (f) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122; (h) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (i) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (j) A method for detecting a polynucleotide that is hybridized with any one of the polynucleotides (f) to (i) under stringent conditions. hybridizing polynucleotides, The chimeric antigen receptor agonist according to (4) or (5), further comprising a polynucleotide selected from the group consisting of: tt.

[0039] (7) The nucleic acid contains miR-4417, miR-4707-5p, miR-7847-3 p, 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-7108-5 p, 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 iR-557, miR-4673, miR-4674, miR-4442, miR-19 15-3p, miR-4687-3p, and miR-92b-3p. and further comprising a nucleic acid capable of specifically binding to at least one or more polynucleotides selected from the group consisting of: 10. The kit according to any one of (1) to (6).

[0040] (8) miR-4417 is hsa-miR-4417, and miR-4707-5p is hsa-miR-4707-5p and miR-7847-3p are hsa-miR-7 847-3p, miR-2861 is hsa-miR-2861, and miR-4 513 is hsa-miR-4513, and miR-7111-5p is hsa-miR- 7111-5p, and miR-6777-5p is hsa-miR-6777-5p. miR-7113-3p is hsa-miR-7113-3p, and miR-464 8 is hsa-miR-4648, and miR-3184-5p is hsa-miR-31 84-5p, miR-4271 is hsa-miR-4271, and miR-67 91-5p is hsa-miR-6791-5p, and miR-642a-3p is hsa -miR-642a-3p and miR-7108-5p are hsa-miR-7108 -5p, and miR-128-1-5p is hsa-miR-128-1-5p; miR-5196-5p is hsa-miR-5196-5p, and miR-3178 is hsa-miR-3178 and miR-3656 are hsa-miR-3656 , miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-67 69b-5p is hsa-miR-6769b-5p, and miR-4689 is hsa- miR-4689, miR-6076 is hsa-miR-6076, and miR -92b-5p is hsa-miR-92b-5p, and miR-6774-5p is hs a-miR-6774-5p and miR-486-3p are hsa-miR-486- 3p, miR-6806-5p is hsa-miR-6806-5p, and miR -6842-5p is hsa-miR-6842-5p, and miR-6716-5p is hsa-miR-6716-5p and miR-557 miR-4673 is hsa-miR-4673, and miR-4674 is hsa- miR-4674, miR-4442 is hsa-miR-4442, and miR -1915-3p is hsa-miR-1915-3p, and miR-4687-3p is hsa-miR-4687-3p and miR-92b-3p are hsa-miR The kit according to (7), wherein the kit is -92b-3p.

[0041] (9) The nucleic acid is a polynucleotide represented by any one of the following (k) to (o): (k) a base sequence represented by any one of SEQ ID NOs: 349 to 383 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 349 to 383; (m) a base sequence represented by any one of SEQ ID NOs: 349 to 383 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (n) a base sequence represented by any one of SEQ ID NOs: 349 to 383 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (o) a polynucleotide that binds to any one of the polynucleotides (k) to (n) under stringent conditions; hybridizing polynucleotides, The chimeric antigen receptor agonist according to (7) or (8), further comprising a polynucleotide selected from the group consisting of: tt.

[0042] (10) The kit includes a pancreatic cancer marker selected from all of the pancreatic cancer markers described in (1) or (2). At least one polynucleotide capable of specifically binding to each of at least two or more polynucleotides The kit according to any one of (1) to (9), comprising two or more nucleic acids.

[0043] (11) pancreatic cancer markers, miR-6893-5p, miR-6075, and miR -6820-5p、miR-4294、miR-6729-5p、miR-4476、m iR-6836-3p、miR-6765-3p、miR-6799-5p、miR-4 530, miR-7641, miR-4454, miR-615-5p, miR-807 3、miR-663a、miR-4634、miR-4450、miR-4792、mi R-665、miR-7975、miR-7109-5p、miR-6789-5p、m iR-4497、miR-6877-5p、miR-6880-5p、miR-7977 miR-4734, miR-6821-5p, miR-8089, miR-5585- 3p、miR-6085、miR-6845-5p、miR-4651、miR-443 3-3p、miR-1231、miR-4665-5p、miR-7114-5p、mi R-1238-5p、miR-8069、miR-4732-5p、miR-619-5 p、miR-3622a-5p、miR-1260a、miR-6741-5p、miR -6781-5p、miR-6125、miR-6805-5p、miR-6132、m iR-6872-3p、miR-6875-5p、miR-1908-3p、miR-4 433b-3p、miR-4736、miR-5100、miR-6724-5p、mi R-7107-5p、miR-6726-5p、miR-3185、miR-4638- 5p、miR-1273g-3p、miR-6778-5p、miR-328-5p、m iR-3679-3p、miR-1228-3p、miR-6779-5p、miR-4 723-5p、miR-6850-5p、miR-760、miR-7704、miR- 8072, miR-4486, miR-1913, miR-4656, miR-1260 b, miR-7106-5p, miR-6889-5p, miR-6780b-5p, m iR-6090, miR-4534, miR-4449, miR-5195-3p, mi R-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-122 7-5p, miR-6722-3p, miR-4286, miR-4746-3p, mi R-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-6757-5p , miR-3131, miR-1343-3p, miR-6775-5p, miR-68 At least one or more selected from the group consisting of miR-13-5p, miR-3940-5p, and miR-3940-5p. A device for detecting pancreatic cancer, comprising a nucleic acid capable of specifically binding to the above polynucleotide.

[0044] (12) miR-6893-5p is hsa-miR-6893-5p, and miR-6 075 is hsa-miR-6075, and miR-6820-5p is hsa-miR- 6820-5p, miR-4294 is hsa-miR-4294, and miR- 6729-5p is hsa-miR-6729-5p, and miR-4476 is hsa- miR-4476 and miR-6836-3p are hsa-miR-6836-3p. miR-6765-3p is hsa-miR-6765-3p, and miR-67 99-5p is hsa-miR-6799-5p, and miR-4530 is hsa-mi miR-4530, miR-7641 is hsa-miR-7641, and miR-4 454 is hsa-miR-4454, and miR-615-5p is hsa-miR-6 15-5p, miR-8073 is hsa-miR-8073, and miR-66 3a is hsa-miR-663a and miR-4634 is hsa-miR-4634 , miR-4450 is hsa-miR-4450, and miR-4792 is hs a-miR-4792, miR-665 is hsa-miR-665, and miR -7975 is hsa-miR-7975, and miR-7109-5p is hsa-mi miR-7109-5p and miR-6789-5p is hsa-miR-6789-5p , miR-4497 is hsa-miR-4497, and miR-6877-5p is hsa-miR-6877-5p, and miR-6880-5p is hsa-miR- 6880-5p, miR-7977 is hsa-miR-7977, and miR- 4734 is hsa-miR-4734 and miR-6821-5p is hsa-miR -6821-5p, miR-8089 is hsa-miR-8089, and miR -5585-3p is hsa-miR-5585-3p, and miR-6085 is hsa -miR-6085 and miR-6845-5p is hsa-miR-6845-5p , miR-4651 is hsa-miR-4651, and miR-4433-3p is hsa-miR-4433-3p, and miR-1231 is hsa-miR-123 1, miR-4665-5p is hsa-miR-4665-5p, and miR- 7114-5p is hsa-miR-7114-5p, and miR-1238-5p is h sa-miR-1238-5p and miR-8069 is hsa-miR-8069 miR-4732-5p is hsa-miR-4732-5p, and miR-61 9-5p is hsa-miR-619-5p, and miR-3622a-5p is hsa- miR-3622a-5p and miR-1260a are hsa-miR-1260a miR-6741-5p is hsa-miR-6741-5p, and miR-67 81-5p is hsa-miR-6781-5p, and miR-6125 is hsa-mi miR-6125, and miR-6805-5p is hsa-miR-6805-5p , miR-6132 is hsa-miR-6132, and miR-6872-3p is hs a-miR-6872-3p and miR-6875-5p are hsa-miR-687 5-5p, miR-1908-3p is hsa-miR-1908-3p, and m iR-4433b-3p is hsa-miR-4433b-3p, and miR-4736 is hsa-miR-4736 and miR-5100 is hsa-miR-5100 miR-6724-5p is hsa-miR-6724-5p, and miR-710 7-5p is hsa-miR-7107-5p, and miR-6726-5p is hsa- miR-6726-5p, miR-3185 is hsa-miR-3185, miR-4638-5p is hsa-miR-4638-5p, and miR-1273g -3p is hsa-miR-1273g-3p, and miR-6778-5p is hsa- miR-6778-5p and miR-328-5p is hsa-miR-328-5p , miR-3679-3p is hsa-miR-3679-3p, and miR-1 228-3p is hsa-miR-1228-3p, and miR-6779-5p is hs a-miR-6779-5p and miR-4723-5p are hsa-miR-472 3-5p, miR-6850-5p is hsa-miR-6850-5p, and m iR-760 is hsa-miR-760, and miR-7704 is hsa-miR-7 704, miR-8072 is hsa-miR-8072, and miR-4486 is hsa-miR-4486 and miR-1913 is hsa-miR-1913 miR-4656 is hsa-miR-4656, and miR-1260b is hsa -miR-1260b and miR-7106-5p is hsa-miR-7106-5 p, miR-6889-5p is hsa-miR-6889-5p, and miR- 6780b-5p is hsa-miR-6780b-5p, and miR-6090 is hs a-miR-6090, miR-4534 is hsa-miR-4534, and m iR-4449 is hsa-miR-4449, and miR-5195-3p is hsa- miR-5195-3p, miR-1202 is hsa-miR-1202, miR-4467 is hsa-miR-4467, and miR-6515-3p is hsa -miR-6515-3p, and miR-4281 is hsa-miR-4281 , miR-4505 is hsa-miR-4505, and miR-4484 is hsa-m iR-4484 and miR-6805-3p is hsa-miR-6805-3p miR-3135b is hsa-miR-3135b, and miR-3162-5p is hsa-miR-3162-5p, and miR-6768-5p is hsa-miR- 6768-5p, and miR-6721-5p is hsa-miR-6721-5p. miR-1227-5p is hsa-miR-1227-5p, and miR-672 2-3p is hsa-miR-6722-3p, and miR-4286 is hsa-miR -4286, and miR-4746-3p is hsa-miR-4746-3p; miR-6727-5p is hsa-miR-6727-5p, and miR-6816- 5p is hsa-miR-6816-5p, and miR-4741 is hsa-miR-4 741, miR-4508 is hsa-miR-4508, and miR-940 is hsa-miR-940 and miR-4327 is hsa-miR-4327; miR-4665-3p is hsa-miR-4665-3p, and miR-718 is h sa-miR-718, miR-1203 is hsa-miR-1203, and m iR-663b is hsa-miR-663b, and miR-4258 is hsa-miR -4258, and miR-4649-5p is hsa-miR-4649-5p; miR-4516 is hsa-miR-4516, and miR-3619-3p is hsa -miR-3619-3p and miR-6826-5p are hsa-miR-6826 -5p, miR-6757-5p is hsa-miR-6757-5p, and mi R-3131 is hsa-miR-3131, and miR-1343-3p is hsa-m iR-1343-3p and miR-6775-5p are hsa-miR-6775-5 p, miR-6813-5p is hsa-miR-6813-5p, and m The device according to (11), wherein iR-3940-5p is hsa-miR-3940-5p. Chair.

[0045] (13) The nucleic acid is a polynucleotide represented by any one of the following (a) to (e): (a) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A polynucleotide consisting of a base sequence or a base sequence in which u is t , a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (b) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 a polynucleotide comprising a base sequence; (c) Represented by any of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A base sequence that is complementary to a base sequence in which u is replaced by t. a polynucleotide containing 15 or more consecutive bases, a variant thereof, a derivative thereof, or a sequence thereof containing 15 or more consecutive bases piece, (d) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 Contains a base sequence or a base sequence complementary to the base sequence in which u is replaced by t polynucleotides, and (e) A polynucleotide that binds to any one of the polynucleotides (a) to (d) under stringent conditions. hybridizing polynucleotides, The device according to (11) or (12), which is a polynucleotide selected from the group consisting of Chair.

[0046] (14) The device is capable of detecting another pancreatic cancer marker, miR-125a-3p, mi R-204-3p, miR-1469, miR-575, miR-150-3p, miR -423-5p, miR-564, miR-3188, miR-1246, miR-60 2, miR-1290, miR-16-5p, miR-451a, miR-24-3p, miR-187-5p, miR-1908-5p, miR-371a-5p and miR- 550a-5p and at least one or more polynucleotides selected from the group consisting of The device according to any one of (11) to (13), further comprising a nucleic acid capable of specifically binding.

[0047] (15) miR-125a-3p is hsa-miR-125a-3p, and miR-2 04-3p is hsa-miR-204-3p, and miR-1469 is hsa-miR -1469, miR-575 is hsa-miR-575, and miR-150- 3p is hsa-miR-150-3p, and miR-423-5p is hsa-miR- 423-5p, miR-564 is hsa-miR-564, and miR-318 8 is hsa-miR-3188 and miR-1246 is hsa-miR-1246 miR-602 is hsa-miR-602, and miR-1290 is hsa-m miR-1290, miR-16-5p is hsa-miR-16-5p, and mi R-451a is hsa-miR-451a, and miR-24-3p is hsa-miR -24-3p, miR-187-5p is hsa-miR-187-5p, and m iR-1908-5p is hsa-miR-1908-5p and miR-371a-5 p is hsa-miR-371a-5p, and miR-550a-5p is hsa- The device according to (14), wherein the miR-550a-5p is miR-550a-5p.

[0048] (16) The nucleic acid is a polynucleotide represented by any one of the following (f) to (j): (f) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122; (h) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (i) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (j) A method for detecting a polynucleotide that is hybridized with any one of the polynucleotides (f) to (i) under stringent conditions. hybridizing polynucleotides, The device according to (14) or (15), which is a polynucleotide selected from the group consisting of Chair.

[0049] (17) The device detects other pancreatic cancer markers, such as miR-4417 and miR-4 707-5p, miR-7847-3p, miR-2861, miR-4513, miR -7111-5p, miR-6777-5p, miR-7113-3p, miR-464 8, miR-3184-5p, miR-4271, miR-6791-5p, miR-6 42a-3p, miR-7108-5p, miR-128-1-5p, miR-5196 -5p, miR-3178, miR-3656, miR-92a-2-5p, miR-6 769b-5p, miR-4689, miR-6076, miR-92b-5p, miR -6774-5p, miR-486-3p, miR-6806-5p, miR-6842 -5p, miR-6716-5p, miR-557, miR-4673, miR-467 4, miR-4442, miR-1915-3p, miR-4687-3p and miR- 92b-3p The device according to any one of (11) to (16), further comprising a nucleic acid capable of binding to

[0050] (18) miR-4417 is hsa-miR-4417, and miR-4707-5p is hsa-miR-4707-5p, and miR-7847-3p is hsa-miR- 7847-3p, miR-2861 is hsa-miR-2861, and miR- 4513 is hsa-miR-4513, and miR-7111-5p is hsa-miR -7111-5p, and miR-6777-5p is hsa-miR-6777-5p. miR-7113-3p is hsa-miR-7113-3p, and miR-46 48 is hsa-miR-4648, and miR-3184-5p is hsa-miR-3 184-5p, miR-4271 is hsa-miR-4271, and miR-6 791-5p is hsa-miR-6791-5p, and miR-642a-3p is hs a-miR-642a-3p and miR-7108-5p are hsa-miR-710 8-5p, miR-128-1-5p is hsa-miR-128-1-5p , miR-5196-5p is hsa-miR-5196-5p, and miR-3178 is hsa-miR-3178 and miR-3656 is hsa-miR-3656 miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-6 769b-5p is hsa-miR-6769b-5p, and miR-4689 is hsa -miR-4689 and miR-6076 are hsa-miR-6076, and mi R-92b-5p is hsa-miR-92b-5p, and miR-6774-5p is h sa-miR-6774-5p and miR-486-3p are hsa-miR-486 -3p, miR-6806-5p is hsa-miR-6806-5p, and mi R-6842-5p is hsa-miR-6842-5p, and miR-6716-5p is hsa-miR-6716-5p and miR-557 is hsa-miR-557 miR-4673 is hsa-miR-4673 and miR-4674 is hsa -miR-4674, miR-4442 is hsa-miR-4442, and mi R-1915-3p is hsa-miR-1915-3p, and miR-4687-3p is hsa-miR-4687-3p, and miR-92b-3p is hsa-mi The device according to (17), which is R-92b-3p.

[0051] (19) The nucleic acid is a polynucleotide represented by any one of the following (k) to (o): (k) a base sequence represented by any one of SEQ ID NOs: 349 to 383 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 349 to 383; (m) a base sequence represented by any one of SEQ ID NOs: 349 to 383 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (n) a base sequence represented by any one of SEQ ID NOs: 349 to 383 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (o) a polynucleotide that binds to any one of the polynucleotides (k) to (n) under stringent conditions; hybridizing polynucleotides, The device according to (17) or (18), which is a polynucleotide selected from the group consisting of Chair.

[0052] (20) The device is a device for measurement by hybridization technology. The device according to any one of (11) to (19).

[0053] (21) The method according to (20), wherein the hybridization technique is a nucleic acid array technique. device.

[0054] (22) The device comprises: A small number of polynucleotides capable of specifically binding to each of at least two or more selected polynucleotides. The device according to any one of (11) to (21), comprising at least two or more nucleic acids.

[0055] (23) The kit according to any one of (1) to (10) or (11) to (22). The expression level of a target nucleic acid in a specimen of a subject is measured using the device described in The expression levels measured and the control expression levels measured in similarly healthy individuals were used to determine whether the subject had pancreatic cancer. To assess in vitro whether a patient has or is not affected by pancreatic cancer A method for detecting pancreatic cancer, comprising:

[0056] (24) The method according to (23), wherein the subject is a human.

[0057] (25) The method according to (23) or (24), wherein the sample is blood, serum, or plasma. .

[0058] <Terminology> Terms used herein have the following definitions.

[0059] As used herein, the term "pancreatic cancer" refers to any malignant tumor that forms in the pancreas. Specifically, serous cystadenocarcinoma, mucinous cystadenocarcinoma, intraductal papillary mucinous adenocarcinoma, invasive ductal carcinoma of the pancreas, These include acinar cell carcinoma, neuroendocrine carcinoma, etc. ("Pancreatic Cancer Guidelines," 6th revised edition, 20 2013, Japan Pancreas Society, Kanehara Publishing, pp. 21-22).

[0060] As used herein, "benign tumors and / or benign diseases of the pancreas and / or surrounding pancreatic organs" means It refers to non-malignant tumors of the pancreas, liver, and biliary tract.

[0061] As used herein, the terms "nucleotide," "polynucleotide," "DNA," The use of abbreviations such as "RNA" is prohibited in the preparation of specifications containing nucleotide sequences or amino acid sequences. Guidelines for Patent Literature" (edited by the Japan Patent Office) and common practice in the art. do.

[0062] As used herein, the term "polynucleotide" refers to RNA, DNA, and RNA / DNA ( The term "DNA" refers to nucleic acids that include both cDNA and chimeric DNA. The above-mentioned RNA includes total DNA, genomic DNA, and synthetic DNA. l RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA In this specification, the term "RNA" includes both non-coding RNA and synthetic RNA. "Synthetic DNA" and "synthetic RNA" are defined as those that contain a specific base sequence (either a natural sequence or a non-natural sequence). ) can be artificially produced using, for example, an automatic nucleic acid synthesizer. As used herein, the term "non-natural sequence" is used in a broad sense. and which differ from the native sequence by, for example, one or more nucleotide substitutions, deletions, Sequences containing insertions and / or additions (i.e., mutant sequences), including one or more modified nucleotides In addition, the term "polynucleotide" as used herein includes sequences containing the polynucleotides (i.e., modified sequences), etc. The term nucleic acid is used interchangeably with nucleic acid.

[0063] As used herein, the term "fragment" refers to a fragment having a continuous partial base sequence of a polynucleotide. It is a polynucleotide having 15 or more bases, preferably 17 or more bases, and more preferably 1 It is desirable that the length be 9 bases or more.

[0064] As used herein, the term "gene" refers not only to RNA and double-stranded DNA, but also to any of the components thereof. Each strand contains a single strand of DNA, such as the positive strand (or sense strand) or the complementary strand (or antisense strand). The term "subject matter" is intended to encompass all subjects, and is not particularly limited by its length.

[0065] Therefore, in this specification, unless otherwise specified, the term "gene" includes human genomic DNA. Double-stranded DNA, single-stranded DNA (positive strand), and single-stranded DNA with a sequence complementary to the positive strand (complementary strand, including cDNA), microRNA (miRNA), and fragments thereof, The term "gene" includes any of a specific base sequence (or sequence number). Not only are genes represented by the numbers (genes) but also the RNAs and biological Functionally equivalent RNAs, such as homologs (i.e., homologs or orthologs), "Nucleic acids" encoding variants, such as genetic polymorphisms, and derivatives are included. The "nucleic acid" encoding the mutant or derivative specifically includes a nucleic acid encoding the stringent A nucleotide sequence represented by any one of SEQ ID NOs: 1 to 499, or a salt thereof, under mild conditions. The base sequence has a base sequence that hybridizes with the complementary sequence of the base sequence in which u is t. The term "gene" does not refer to any specific functional region. It may include, for example, an expression control region, a coding region, an exon, or an intron. Furthermore, a "gene" may be contained within a cell, or may be released outside the cell and exist independently. They may also be encapsulated in small vesicles called exosomes.

[0066] As used herein, "exosomes" (also known as "exosomes") are molecules secreted from cells. Exosomes are small vesicles enclosed in a lipid bilayer membrane. They originate from multivesicular endosomes and are extracellular. When released into the environment, they lose internal biological substances such as genes (e.g., RNA and DNA) and proteins. Exosomes are found in bodily fluids such as blood, serum, plasma, and lymph. is known.

[0067] As used herein, the term "transcription product" refers to a RNA synthesized using the DNA sequence of a gene as a template. A refers to the region called the promoter upstream of the gene where RNA polymerase is located. and binds to the 3' end of the DNA, and binds a ribonucleotide to the 3' end so that it is complementary to the base sequence of the DNA. This RNA contains not only the gene itself but also the the region from the transcription start site to the poly(A) sequence, including the coding region, exon or intron The entire sequence is included, all the way to the termini.

[0068] In addition, in this specification, unless otherwise specified, "microRNA (miRNA)" means It is transcribed as a hairpin-like RNA precursor and has RNase III cleavage activity. It is cleaved by sRNA cleavage enzymes and incorporated into a protein complex called RISC, Non-coding RNAs of 15 to 25 bases involved in RNA translational repression are used intentionally. Furthermore, as used herein, "miRNA" is represented by a specific base sequence (or SEQ ID NO:). In addition to the miRNAs themselves, we also study the precursors of these miRNAs (pre-miRNAs, p ri-miRNAs), and miRNAs with equivalent biological functions, e.g., homologs ( It also includes variants such as homologs or orthologs, genetic polymorphisms, and derivatives. Such precursors, homologues, variants or derivatives include, in particular, those listed in the miRBase Identified by release 20 (http: / / www.mirbase.org / ) Any of SEQ ID NOs: 1 to 499 can be isolated under the stringent conditions described below. A nucleic acid sequence that hybridizes with the complementary sequence of any of the specific nucleic acid sequences represented by Furthermore, the term "miRNA" as used herein can be used to refer to a specific miRNA. " may be a gene product of a miR gene, and such a gene product is a mature miR NA (for example, 15 to 25 bases involved in the translational repression of mRNA as described above, or 19 to 25 bases, non-coding RNA) or miRNA precursor (e.g., pr miRNAs (e-miRNA or pri-miRNA).

[0069] As used herein, the term "probe" refers to RNA generated by gene expression or a probe derived therefrom. Polynucleotides and / or includes polynucleotides complementary thereto.

[0070] As used herein, the term "primer" refers to an RNA generated by gene expression or a primer therefor. A polynucleotide that specifically recognizes and amplifies the polynucleotide from which it is derived and / or The present invention encompasses polynucleotides complementary to the sequences of the sequences of the present invention.

[0071] Here, the complementary polynucleotide (complementary strand, reverse strand) is any one of SEQ ID NOs: 1 to 499. a base sequence defined by the above formula, or a base sequence in which u is t; The full-length sequence of a polynucleotide consisting of the above, or a partial sequence thereof (for convenience, this is referred to as the correct sequence here) base-complementary to the nucleotide sequence (called the "strand") based on base pairing relationships such as A:T(U) and G:C The term "complementary strand" refers to a polynucleotide that is in a complementary relationship to the target strand. It is not limited to cases where the base sequence is completely complementary to the target positive strand. The complementary relationship may be such that the hybridization occurs under certain conditions.

[0072] As used herein, "stringent conditions" refers to conditions under which a nucleic acid probe is highly sensitive to other sequences. to a detectably greater extent (e.g., the average of background measurements plus background The number of hybridizations to the target sequence is determined by the number of hybridizations (measurements of at least 2 times the standard error of the round measurement). Stringent conditions are sequence-dependent and are conditions under which hybridization is The stringency of hybridization and / or washing conditions varies depending on the environment in which they are performed. By controlling the gene expression, a target sequence that is 100% complementary to the nucleic acid probe is obtained. Specific examples of "stringent conditions" are described below.

[0073] As used herein, the term "Tm value" refers to the time at which the double-stranded portion of a polynucleotide is denatured into a single strand. means the temperature at which double-stranded and single-stranded molecules exist in a 1:1 ratio.

[0074] As used herein, the term "variant" refers to a naturally occurring variant of a nucleic acid resulting from polymorphism, mutation, etc. or a variant thereof, or any of the base sequences of SEQ ID NOs: 1 to 499, or In the base sequence in which u is t, or in a partial sequence thereof, one or more bases are deleted or substituted. a mutant containing a substitution, addition or insertion, or a nucleotide sequence or a partial sequence thereof, and % or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more percent identity Variants, or polynucleotides or oligonucleotides containing the base sequence or a partial sequence thereof The term "nucleotide sequence" refers to a nucleic acid that hybridizes with a target nucleic acid under stringent conditions as defined above.

[0075] As used herein, "several" refers to an integer of about 10, 9, 8, 7, 6, 5, 4, 3, or 2. means.

[0076] As used herein, the term "mutant" refers to a mutation obtained by site-directed mutagenesis or PCR. They can be produced using well-known techniques such as heterotransferase.

[0077] As used herein, "% identity" refers to the percentage of identity between proteins or sequences as determined by BLAST or FASTA as described above. using a gene search system, with or without introducing gaps, can be determined (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, p. 203-214; Altschul, S.F. et al., 1990 , Journal of Molecular Biology, Vol. 215, p. 403 -410; Pearson, WR et al., 1988, Proc. Natl. Aca d. Sci. USA, Vol. 85, p2444-2448).

[0078] As used herein, the term "derivative" refers to a modified nucleic acid, for example, but not limited to, labeling with a fluorophore or the like. modified nucleotides (e.g., halogenated, alkyl, such as methyl, methoxy, etc.); Reconstruction of nucleotides and bases containing alkoxy, thio, carboxymethyl, etc. groups nucleotides that have undergone double bond saturation, deamination, and substitution of oxygen molecules with sulfur molecules derivatives including PNA (peptide nucleic acid; Niel Sen, PE et al., 1991, Science, Vol. 254, pp. 1497-500) , LNA (locked nucleic acid; Obika, S. et al., 1998 Tetrahedron Lett., Vol. 39, p. 5401-5404) This means that

[0079] As used herein, a polynucleotide selected from the miRNAs that are pancreatic cancer markers is The "nucleic acid" capable of specifically binding to a nucleic acid is a synthetic or prepared nucleic acid, specifically A method for detecting the presence or absence of pancreatic cancer in a subject, comprising a "nucleic acid probe" or "primer" or to determine whether or not a patient has pancreatic cancer, the extent of the disease, and whether or not the patient has improved in pancreatic cancer and the extent of improvement. , for diagnosing sensitivity to treatment of pancreatic cancer, or for preventing, ameliorating or preventing pancreatic cancer. It can be used directly or indirectly to screen for candidate substances useful in therapy. Furthermore, in vivo, particularly in samples of body fluids such as blood and urine, sequence numbers related to the onset of pancreatic cancer have been found. The transcription product represented by any one of Nos. 1 to 499 or its cDNA synthetic nucleic acid is specifically recognized. nucleotides, oligonucleotides and polynucleotides that can be linked together. These nucleotides, oligonucleotides and polynucleotides have the above properties. Based on this, it can be used as a probe to detect the above genes expressed in vivo, in tissues, cells, etc. Furthermore, it can be effectively used as a primer for amplifying the above gene expressed in vivo. This can be done.

[0080] The term "detection" as used herein means inspection, measurement, detection, or decision support. In addition, the term "evaluation" as used herein refers to test results or measurement results. It is used to include assisting in diagnosis or evaluation based on the above.

[0081] As used herein, a "subject" refers to a human, a primate, including a chimpanzee, a dog, a cat, or the like. Any pet animals, livestock animals such as cows, horses, sheep, goats, rodents such as mice and rats A "healthy individual" also refers to such a mammal, It means an animal that is not affected by the cancer to be detected.

[0082] As used herein, "P" or "P value" refers to the probability that a statistical test will yield a positive result under the null hypothesis. indicates the probability that a statistic more extreme than the statistic calculated from the actual data will be observed. Therefore, the smaller the "P" or "P value," the more significant the difference between the compared subjects.

[0083] As used herein, "sensitivity" refers to the value of (the number of true positives) / (the number of true positives + the number of false negatives). High sensitivity makes it possible to detect pancreatic cancer early and to identify the complete cancer site. This leads to a reduction in resection and recurrence rates.

[0084] As used herein, "specificity" means (number of true negatives) / (number of true negatives + number of false positives). High specificity would prevent unnecessary additional testing due to misclassification of healthy subjects as pancreatic cancer patients. This will prevent the implementation of the procedure, reducing the burden on patients and cutting medical costs.

[0085] In this specification, "accuracy" means the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy indicates the percentage of all samples for which the discrimination results were correct, and is used to evaluate detection performance. This will be the first indicator.

[0086] In this specification, the "specimen" to be determined, detected or diagnosed is a specimen that is used to determine the occurrence of pancreatic cancer, The expression of the gene of the present invention changes with the progression of cancer and the effect of treatment on pancreatic cancer. Specifically, it refers to pancreatic tissue and its surrounding blood vessels, lymph nodes, and organs. organs, organs suspected of metastasis, skin, and bodily fluids such as blood, urine, saliva, sweat, and tissue exudates, This refers to serum and plasma prepared from blood, as well as feces, hair, etc. This refers to biological samples, specifically genes such as RNA and miRNA.

[0087] As used herein, "hsa-miR-6893-5p gene" or "hsa-mi The term "miR-6893-5p" refers to hsa-miR-6893-5p as set forth in SEQ ID NO: 1. p gene (miRBase Accession No. MIMAT0027686) Other species homologs or orthologs are also included. hsa-miR-6893 The -5p gene is Ladewig E et al., 2012, Genome Res., Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6893-5p has a hairpin-like structure as its precursor, hsa-mir -6893" (miRBase Accession No. MI0022740, sequence Number 123) is known.

[0088] As used herein, "hsa-miR-6075 gene" or "hsa-miR-6 The term "miR-6075" refers to the hsa-miR-6075 gene (miRB) set forth in SEQ ID NO: 2. ase Accession No. MIMAT0023700) and other species homologues The hsa-miR-6075 gene is also included in the Voel Lenkle C et al., 2012, RNA., Vol. 18, p. 472-484 hsa-miR-6075 can be obtained by the method described above. The miRBase Accession No. 100002666666 (hsa-mir-6075) (miRBase Accession No. 1000026 ...) forms a hairpin-like structure. Ion No. MI0020352, SEQ ID NO: 124) is known.

[0089] As used herein, "hsa-miR-6820-5p gene" or "hsa-mi The term "miR-6820-5p" refers to hsa-miR-6820-5p as set forth in SEQ ID NO: 3. p gene (miRBase Accession No. MIMAT0027540) Other species homologs or orthologs are also included. hsa-miR-6820 The -5p gene is Ladewig E et al., 2012, Genome Res., Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6820-5p has a hairpin-like structure as its precursor, hsa-mir -6820" (miRBase Accession No. MI0022665, sequence Number 125) is known.

[0090] As used herein, "hsa-miR-4294 gene" or "hsa-miR-4 The term "miR-4294" refers to the hsa-miR-4294 gene (miRB294) set forth in SEQ ID NO: 4. ase Accession No. MIMAT0016849) and other species homologues The hsa-miR-4294 gene is a member of the Goff According to the method described in LA et al., 2009, PLoS One., Vol. 4, e7192 In addition, "hsa-miR-4294" can be obtained by using hairpin as its precursor. The miRBase Accession No. 100001266666 (hsa-mir-4294) has a miR-like structure. No. MI0015827, SEQ ID NO: 126) are known.

[0091] As used herein, "hsa-miR-6729-5p gene" or "hsa-mi The term "miR-6729-5p" refers to hsa-miR-6729-5p as set forth in SEQ ID NO: 5. p gene (miRBase Accession No. MIMAT0027359) Other species homologs or orthologs are also included. hsa-miR-6729 The -5p gene is Ladewig E et al., 2012, Genome Res., Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6729-5p has a hairpin-like structure as its precursor, hsa-mir -6729" (miRBase Accession No. MI0022574, sequence Number 127) is known.

[0092] As used herein, "hsa-miR-4476 gene" or "hsa-miR-4 The term "miR-4476" refers to the hsa-miR-4476 gene (miRB) set forth in SEQ ID NO: 6. ase Accession No. MIMAT0019003) and other species homologues The hsa-miR-4476 gene is also included in the Jima The method described in DD et al., 2010, Blood., Vol. 116, e118-e127 Furthermore, "hsa-miR-4476" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4476" (miRBase Accession No. on No. MI0016828, SEQ ID NO: 128) is known.

[0093] As used herein, the term "hsa-miR-6836-3p gene" or "hsa-mi The term "miR-6836-3p" refers to hsa-miR-6836-3p as set forth in SEQ ID NO: 7. p gene (miRBase Accession No. MIMAT0027575) Other species homologs or orthologs are also included. hsa-miR-6836 The -3p gene is Ladewig E et al., 2012, Genome Res., Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6836-3p has a hairpin-like structure as its precursor, hsa-mir -6836" (miRBase Accession No. MI0022682, sequence Number 129) is known.

[0094] As used herein, "hsa-miR-6765-3p gene" or "hsa-mi The term "miR-6765-3p" refers to hsa-miR-6765-3p as set forth in SEQ ID NO: 8. p gene (miRBase Accession No. MIMAT0027431) Other species homologs or orthologs are also included. hsa-miR-6765 The -3p gene is Ladewig E et al., 2012, Genome Res., Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6765-3p has a hairpin-like structure as its precursor, hsa-mir -6765" (miRBase Accession No. MI0022610, sequence Number 130) is known.

[0095] As used herein, "hsa-miR-6799-5p gene" or "hsa-mi The term "miR-6799-5p" refers to hsa-miR-6799-5p as set forth in SEQ ID NO: 9. p gene (miRBase Accession No. MIMAT0027498) Other species homologs or orthologs are also included. hsa-miR-6799 The -5p gene is Ladewig E et al., 2012, Genome Res., Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6799-5p has a hairpin-like structure as its precursor, hsa-mir -6799" (miRBase Accession No. MI0022644, sequence Number 131) is known.

[0096] As used herein, "hsa-miR-4530 gene" or "hsa-miR-4 The term "miR-4530" refers to the hsa-miR-4530 gene (miR Base Accession No. MIMAT0019069) and other species of Homo sapiens The hsa-miR-4530 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4530 can be obtained by the method described above. The miRBase Accession No. 1000266666 (hsa-mir-4530) forms a hairpin-like structure. ion No. MI0016897, SEQ ID NO: 132) is known.

[0097] As used herein, "hsa-miR-7641 gene" or "hsa-miR-7 The term "miR-7641" refers to the hsa-miR-7641 gene (miR Base Accession No. MIMAT0029782) and other species of Homo sapiens The hsa-miR-7641 gene is a member of the Yoo JK et al., 2013, Arch Pharm Res. 36, pp. 353-358 hsa-miR-7641 can be obtained by the method described in the The precursors "hsa-mir-7641-1, hsa-mir- 7641-2” (miRBase Accession No. MI0024975, MI0024976, SEQ ID NOs: 133 and 134) are known.

[0098] As used herein, "hsa-miR-4454 gene" or "hsa-miR-4 The term "miR-4454" refers to the hsa-miR-4454 gene (miR Base Accession No. MIMAT0018976) and other species of Homo sapiens The hsa-miR-4454 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4454 can be obtained by the method described above. The miRBase Accession No. 10000266666 (hsa-mir-4454) forms a hairpin-like structure. ion No. MI0016800, SEQ ID NO: 135) is known.

[0099] As used herein, "hsa-miR-615-5p gene" or "hsa-miR The term "miR-615-5p" refers to the hsa-miR-615-5p gene set forth in SEQ ID NO: 13. gene (miRBase Accession No. MIMAT0004804) and its It also includes homologs or orthologs from other species. Genes, Cummins JM, 2006, Proc Natl Acad Sci It can be obtained by the method described in Vol. 103, pp. 3687-3692. "hsa-miR-615-5p" is a precursor of "hsa" which has a hairpin-like structure. -mir-615” (miRBase Accession No. MI0003628 , SEQ ID NO: 136) is known.

[0100] As used herein, "hsa-miR-8073 gene" or "hsa-miR-8 The term "miR-8073" refers to the hsa-miR-8073 gene (miR-8073) set forth in SEQ ID NO: 14. Base Accession No. MIMAT0031000) and other species of Homo sapiens The hsa-miR-8073 gene is a member of the Wan The method described in g HJ et al., 2013, Shock., Vol. 39, p. 480-487 hsa-miR-8073 can be obtained as a precursor of hsa-miR-8073. The miRBase Accession No. 100001266666 (hsa-mir-8073) has an apin-like structure. n No. MI0025909, SEQ ID NO: 137) is known.

[0101] As used herein, "hsa-miR-663a gene" or "hsa-miR-6 The term "miR-663a" refers to the hsa-miR-663a gene (miR Base Accession No. MIMAT0003326) and other species of Homo sapiens The hsa-miR-663a gene is a member of the Cum Mins JM, 2006, Proc Natl Acad Sci, vol. 103, p. 3 The "hsa-miR" can be obtained by the method described in US Pat. -663a" has a hairpin-like structure as its precursor, "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 138) is known.

[0102] As used herein, "hsa-miR-4634 gene" or "hsa-miR-4 The term "miR-4634" refers to the hsa-miR-4634 gene (miR Base Accession No. MIMAT0019691) and other species of Homo sapiens The hsa-miR-4634 gene is a member of the Per sson H et al., 2011, Cancer Res., Vol. 71, p78-86 hsa-miR-4634 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4634" ( Session No. MI0017261, SEQ ID NO: 139) is known.

[0103] As used herein, "hsa-miR-4450 gene" or "hsa-miR-4 The term "miR-4450" refers to the hsa-miR-4450 gene (miR Base Accession No. MIMAT0018971) and other species of Homo sapiens The hsa-miR-4450 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4450 can be obtained by the method described above. The miRBase Accession No. 10000266666 (hsa-mir-4450) has a hairpin-like structure. Ion No. MI0016795, SEQ ID NO: 140) is known.

[0104] As used herein, "hsa-miR-4792 gene" or "hsa-miR-4 The term "miR-4792" refers to the hsa-miR-4792 gene (miR Base Accession No. MIMAT0019964) and other species of Homo sapiens The hsa-miR-4792 gene is a member of the Per sson H et al., 2011, Cancer Res., Vol. 71, p78-86 hsa-miR-4792 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4792" ( Session No. MI0017439, SEQ ID NO: 141) is known.

[0105] As used herein, "hsa-miR-665 gene" or "hsa-miR-66 The term "miR-665" refers to the hsa-miR-665 gene (miRBas) set forth in SEQ ID NO: 19. e Accession No. MIMAT0004952) and homologs in other species The hsa-miR-665 gene is a member of the Berezik ov E et al., 2006, Genome Res., Vol. 16, p1289-1298 hsa-miR-665 can be obtained by the method described in the literature. The miRBase Accelerator, "hsa-mir-665" (miRBase Accelerator), has a hairpin-like structure. Session No. MI0005563, SEQ ID NO: 142) is known.

[0106] As used herein, "hsa-miR-7975 gene" or "hsa-miR-7 The term "miR-7975" refers to the hsa-miR-7975 gene (miR Base Accession No. MIMAT0031178) and other species of Homo sapiens The hsa-miR-7975 gene is a member of the Vel thut-Meikas A et al. 2013. Mol Endocrinol. [Ep It can be obtained by the method described in [pub prior to print]. In addition, "hsa-miR-7975" has a hairpin-like structure as its precursor, "hsa -mir-7975” (miRBase Accession No. MI002575 1, SEQ ID NO: 143) is known.

[0107] As used herein, "hsa-miR-7109-5p gene" or "hsa-mi The term "hsa-miR-7109-5p" refers to hsa-miR-7109- 5p gene (miRBase Accession No. MIMAT0028115) and other species homologs or orthologs. The 9-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-7109-5p has a hairpin-like structure as its precursor, "hsa-mi r-7109" (miRBase Accession No. MI0022960, Column number 144) is known.

[0108] As used herein, "hsa-miR-6789-5p gene" or "hsa-mi The term "miR-6789-5p" refers to hsa-miR-6789-5p as set forth in SEQ ID NO: 22. 5p gene (miRBase Accession No. MIMAT0027478) hsa-miR-678 and other species homologs or orthologs. The 9-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6789-5p has a hairpin-like structure as its precursor, "hsa-mi r-6789" (miRBase Accession No. MI0022634, Column number 145) is known.

[0109] As used herein, "hsa-miR-4497 gene" or "hsa-miR-4 The term "miR-4497" refers to the hsa-miR-4497 gene (miR Base Accession No. MIMAT0019032) and other species of Homo sapiens The hsa-miR-4497 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4497 can be obtained by the method described above. The miRBase Accession No. 1000020 ... ion No. MI0016859, SEQ ID NO: 146) is known.

[0110] As used herein, "hsa-miR-6877-5p gene" or "hsa-mi The term "miR-6877-5p" refers to hsa-miR-6877-5p as set forth in SEQ ID NO: 24. 5p gene (miRBase Accession No. MIMAT0027654) hsa-miR-687 and other species homologs or orthologs. The 7-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6877-5p has a hairpin-like structure as its precursor, "hsa-mi r-6877” (miRBase Accession No. MI0022724, Column number 147) is known.

[0111] As used herein, "hsa-miR-6880-5p gene" or "hsa-mi The term "miR-6880-5p" refers to hsa-miR-6880-5p as set forth in SEQ ID NO: 25. 5p gene (miRBase Accession No. MIMAT0027660) hsa-miR-688 and other species homologs or orthologs. The 0-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6880-5p has a hairpin-like structure as its precursor, "hsa-mi r-6880” (miRBase Accession No. MI0022727, Column number 148) is known.

[0112] As used herein, "hsa-miR-7977 gene" or "hsa-miR-7 The term "miR-7977" refers to the hsa-miR-7977 gene (miR Base Accession No. MIMAT0031180) and other species of Homo sapiens The hsa-miR-7977 gene is a member of the Vel thut-Meikas A et al. 2013. Mol Endocrinol. [Ep It can be obtained by the method described in [pub prior to print]. In addition, "hsa-miR-7977" has a hairpin-like structure as its precursor, "hsa -mir-7977” (miRBase Accession No. MI002575 3, SEQ ID NO: 149) is known.

[0113] As used herein, "hsa-miR-4734 gene" or "hsa-miR-4 The term "miR-4734" refers to the hsa-miR-4734 gene (miR Base Accession No. MIMAT0019859) and other species of Homo sapiens The hsa-miR-4734 gene is a member of the Per sson H et al., 2011, Cancer Res., Vol. 71, p78-86 hsa-miR-4734 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4734" ( Session No. MI0017371, SEQ ID NO: 150) is known.

[0114] As used herein, "hsa-miR-6821-5p gene" or "hsa-mi The term "miR-6821-5p" refers to hsa-miR-6821-5p as set forth in SEQ ID NO: 28. 5p gene (miRBase Accession No. MIMAT0027542) hsa-miR-682 and other species homologs or orthologs. The 1-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6821-5p has a hairpin-like structure as its precursor, "hsa-mi r-6821" (miRBase Accession No. MI0022666, Column number 151) is known.

[0115] As used herein, "hsa-miR-8089 gene" or "hsa-miR-8 The term "miR-8089" refers to the hsa-miR-8089 gene (miR Base Accession No. MIMAT0031016) and other species of Homo sapiens The hsa-miR-8089 gene is a member of the Wan The method described in g HJ et al., 2013, Shock., Vol. 39, p. 480-487 hsa-miR-8089 can be obtained by The miRBase Accession No. 10000266666 (hsa-mir-8089) has an apin-like structure. n No. MI0025925, SEQ ID NO: 152) is known.

[0116] As used herein, "hsa-miR-5585-3p gene" or "hsa-mi The term "miR-5585-3p" refers to hsa-miR-5585-3p as set forth in SEQ ID NO: 30. 3p gene (miRBase Accession No. MIMAT0022286) hsa-miR-558 and other species homologs or orthologs. The 5-3p gene is described in Friedlander MR et al., 2012, Nucleic A cids Res., Vol. 40, pp. 37-52. In addition, "hsa-miR-5585-3p" has a hairpin-like structure as its precursor. The miRBase Accession No. MI0 019142, SEQ ID NO: 153) is known.

[0117] As used herein, "hsa-miR-6085 gene" or "hsa-miR-6 The term "miR-6085" refers to the hsa-miR-6085 gene (miR-6085) set forth in SEQ ID NO: 31. Base Accession No. MIMAT0023710) and other species of Homo sapiens The hsa-miR-6085 gene is a member of the Voe llenkle C et al., 2012, RNA., Vol. 18, p. 472-484 hsa-miR-6085 can be obtained by the method described above. The miRBase Accession No. 100002666666, which has a hairpin-like structure, is sion No. MI0020362, SEQ ID NO: 154) is known.

[0118] As used herein, "hsa-miR-6845-5p gene" or "hsa-mi The term "miR-6845-5p" refers to hsa-miR-6845-5p as set forth in SEQ ID NO: 32. 5p gene (miRBase Accession No. MIMAT0027590) hsa-miR-684 and other species homologs or orthologs. The 5-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6845-5p has a hairpin-like structure as its precursor, "hsa-mi r-6845" (miRBase Accession No. MI0022691, Column number 155) is known.

[0119] As used herein, "hsa-miR-4651 gene" or "hsa-miR-4 The term "miR-4651" refers to the hsa-miR-4651 gene (miR-4651) set forth in SEQ ID NO: 33. Base Accession No. MIMAT0019715) and other species of Homo sapiens The hsa-miR-4651 gene is a member of the Per sson H et al., 2011, Cancer Res., Vol. 71, p78-86 hsa-miR-4651 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure. Session No. MI0017279, SEQ ID NO: 156) is known.

[0120] As used herein, "hsa-miR-4433-3p gene" or "hsa-mi The term "miR-4433-3p" refers to hsa-miR-4433-3p as set forth in SEQ ID NO: 34. 3p gene (miRBase Accession No. MIMAT0018949) hsa-miR-443 and other species homologs or orthologs. The 3-3p gene is described in Jima DD et al., 2010, Blood., Vol. 116, e118 The miR-44 gene can be obtained by the method described in Ref. 33-3p" has a hairpin-like structure as its precursor, "hsa-mir-4433" (miRBase Accession No. MI0016773, SEQ ID NO: 157) is known.

[0121] As used herein, "hsa-miR-1231 gene" or "hsa-miR-1 The term "miR-1231" refers to the hsa-miR-1231 gene (miR-1231) set forth in SEQ ID NO: 35. Base Accession No. MIMAT0005586) and other species of Homo sapiens The hsa-miR-1231 gene is a member of the Ber Ezikov E et al., 2007, Mol Cell., vol. 28, pp. 328-336 hsa-miR-1231 can be obtained by the method described in the The precursor of "hsa-mir-1231" (miRBase A Accession No. MI0006321, SEQ ID NO: 158) is known.

[0122] As used herein, "hsa-miR-4665-5p gene" or "hsa-mi The term "miR-4665-5p" refers to hsa-miR-4665-5p as set forth in SEQ ID NO: 36. 5p gene (miRBase Accession No. MIMAT0019739) hsa-miR-466 and other species homologs or orthologs. The 5-5p gene is Persson H et al., 2011, Cancer Res., 71 The hsa-miR can be obtained by the method described in Vol. -4665-5p is a precursor of hsa-mir-46, which has a hairpin-like structure. 65" (miRBase Accession No. MI0017295, SEQ ID NO: 1 59) is known.

[0123] As used herein, "hsa-miR-7114-5p gene" or "hsa-mi The term "miR-7114-5p" refers to hsa-miR-7114-5p as set forth in SEQ ID NO: 37. 5p gene (miRBase Accession No. MIMAT0028125) hsa-miR-711 and other species homologs or orthologs. The 4-5p genes are described in Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-7114-5p has a hairpin-like structure as its precursor, "hsa-mi r-7114" (miRBase Accession No. MI0022965, Column number 160) is known.

[0124] As used herein, "hsa-miR-1238-5p gene" or "hsa-mi The term "miR-1238-5p" refers to hsa-miR-1238-5p as set forth in SEQ ID NO: 38. 5p gene (miRBase Accession No. MIMAT0022947) hsa-miR-123 and other species homologs or orthologs. The 8-5p gene is described in Berezikov E et al., 2007, Mol Cell., 28 It can be obtained by the method described in Vol. 1, pp. 328-336. iR-1238-5p is a precursor of the hairpin-like structure known as hsa-mir- 1238" (miRBase Accession No. MI0006328, sequence no. No. 161) is known.

[0125] As used herein, "hsa-miR-8069 gene" or "hsa-miR-8 The term "miR-8069" refers to the hsa-miR-8069 gene (miR-8069) set forth in SEQ ID NO: 39. Base Accession No. MIMAT0030996) and other species of Homo sapiens The hsa-miR-8069 gene is a member of the Wan The method described in g HJ et al., 2013, Shock., Vol. 39, p. 480-487 hsa-miR-8069 can be obtained by The miRBase Accession No. hsa-mir-8069 (miRBase Accession No. hsa-mir-8069) has an apin-like structure. n No. MI0025905, SEQ ID NO: 162) is known.

[0126] As used herein, "hsa-miR-4732-5p gene" or "hsa-mi The term "miR-4732-5p" refers to hsa-miR-4732-5p as set forth in SEQ ID NO: 40. 5p gene (miRBase Accession No. MIMAT0019855) hsa-miR-473 and other species homologs or orthologs. The 2-5p gene is Persson H et al., 2011, Cancer Res., 71 The hsa-miR can be obtained by the method described in Vol. -4732-5p is a precursor of hsa-mir-47, which has a hairpin-like structure. 32" (miRBase Accession No. MI0017369, SEQ ID NO: 1 63) is known.

[0127] As used herein, "hsa-miR-619-5p gene" or "hsa-miR The term "miR-619-5p" refers to the hsa-miR-619-5p gene set forth in SEQ ID NO: 41. gene (miRBase Accession No. MIMAT0026622) and its It also includes homologs or orthologs from other species. Genes, Cummins JM, 2006, Proc Natl Acad Sci It can be obtained by the method described in Vol. 103, pp. 3687-3692. "hsa-miR-619-5p" is a precursor of "hsa" which has a hairpin-like structure. -mir-619” (miRBase Accession No. MI0003633 , SEQ ID NO: 164) is known.

[0128] As used herein, "hsa-miR-3622a-5p gene" or "hsa-m The term "miR-3622a-5p" refers to hsa-miR-3622a-5p as set forth in SEQ ID NO: 42. 2a-5p gene (miRBase Accession No. MIMAT00180 03) and other species homologs or orthologs. The 3622a-5p gene is described in Witten D et al., 2010, BMC Biol., 8 The miR-36 gene can be obtained by the method described in Vol. 1, p. 58. 22a-5p is a precursor of hsa-mir-3622, which has a hairpin-like structure. a" (miRBase Accession No. MI0016013, SEQ ID NO: 16 5) is known.

[0129] As used herein, "hsa-miR-1260a gene" or "hsa-miR- The term "miR-1260a" refers to the hsa-miR-1260a gene ( miRBase Accession No. MIMAT0005911) and other organisms The hsa-miR-1260a gene is a member of the family of miR-1260a. , Morin RD et al., 2008, Genome Res., Vol. 18, p610-62 It can be obtained by the method described in 1. Its precursor, "hsa-mir-1260a" (miRB), has a hairpin-like structure. The enzyme (Accession No. MI0006394, SEQ ID NO: 166) is known There are.

[0130] As used herein, "hsa-miR-6741-5p gene" or "hsa-mi The term "miR-6741-5p" refers to hsa-miR-6741-5p as set forth in SEQ ID NO: 44. 5p gene (miRBase Accession No. MIMAT0027383) hsa-miR-674 and other species homologs or orthologs. The 1-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6741-5p has a hairpin-like structure as its precursor, "hsa-mi r-6741" (miRBase Accession No. MI0022586, Column number 167) is known.

[0131] As used herein, "hsa-miR-6781-5p gene" or "hsa-mi The term "hsa-miR-6781-5p" refers to hsa-miR-6781- 5p gene (miRBase Accession No. MIMAT0027462) hsa-miR-678 and other species homologs or orthologs. The 1-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6781-5p has a hairpin-like structure as its precursor, "hsa-mi r-6781" (miRBase Accession No. MI0022626, Column number 168) is known.

[0132] As used herein, "hsa-miR-6125 gene" or "hsa-miR-6 The term "miR-6125" refers to the hsa-miR-6125 gene (miR-6125) set forth in SEQ ID NO: 46. Base Accession No. MIMAT0024598) and other species of Homo sapiens The hsa-miR-6125 gene is a member of the Smi th JL et al., 2012, J Virol., Vol. 86, p5278-5287 hsa-miR-6125 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure. Session No. MI0021259, SEQ ID NO: 169) is known.

[0133] As used herein, "hsa-miR-6805-5p gene" or "hsa-mi The term "miR-6805-5p" refers to hsa-miR-6805-5p as set forth in SEQ ID NO: 47. 5p gene (miRBase Accession No. MIMAT0027510) hsa-miR-680 and other species homologs or orthologs. The 5-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6805-5p has a hairpin-like structure as its precursor, "hsa-mi r-6805” (miRBase Accession No. MI0022650, Column number 170) is known.

[0134] As used herein, "hsa-miR-6132 gene" or "hsa-miR-6 The term "miR-6132" refers to the hsa-miR-6132 gene (miR-6132) set forth in SEQ ID NO: 48. Base Accession No. MIMAT0024616) and other species of Homo sapiens The hsa-miR-6132 gene is a member of the Dan nemann M, 2012, Genome Biol Evol., vol. 4, p552 The miR-613 can be obtained by the method described in ref. 4. 2” has a hairpin-like structure as its precursor, “hsa-mir-6132” (miR Base Accession No. MI0021277, SEQ ID NO: 171) is known are.

[0135] As used herein, "hsa-miR-6872-3p gene" or "hsa-mi The term "miR-6872-3p" refers to hsa-miR-6872-3p as set forth in SEQ ID NO: 49. 3p gene (miRBase Accession No. MIMAT0027645) hsa-miR-687 and other species homologs or orthologs. The 2-3p genes are described in Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6872-3p has a hairpin-like structure as its precursor, "hsa-mi r-6872” (miRBase Accession No. MI0022719, Column number 172) is known.

[0136] As used herein, "hsa-miR-6875-5p gene" or "hsa-mi The term "miR-6875-5p" refers to hsa-miR-6875- 5p gene (miRBase Accession No. MIMAT0027650) hsa-miR-687 and other species homologs or orthologs. The 5-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6875-5p has a hairpin-like structure as its precursor, "hsa-mi r-6875” (miRBase Accession No. MI0022722, Column number 173) is known.

[0137] As used herein, "hsa-miR-1908-3p gene" or "hsa-mi The term "hsa-miR-1908-3p" refers to hsa-miR-1908- 3p gene (miRBase Accession No. MIMAT0026916) hsa-miR-190 and other species homologs or orthologs. The 8-3p gene is described in Bar M et al., 2008, Stem Cells., Vol. 26, p. 2 The hsa-miR can be obtained by the method described in JP 496-2505. -1908-3p is a precursor of hsa-mir-19, which has a hairpin-like structure. 08" (miRBase Accession No. MI0008329, SEQ ID NO: 1 74) is known.

[0138] As used herein, "hsa-miR-4433b-3p gene" or "hsa-m The term "miR-4433b-3p" refers to hsa-miR-443 3b-3p gene (miRBase Accession No. MIMAT00304 14) and other species homologs or orthologs. The 4433b-3p gene is Ple H et al., 2012, PLoS One., Vol. 7, e The miR-44 gene can be obtained by the method described in 50746. 33b-3p has a hairpin-like structure as its precursor, hsa-mir-4433 b" (miRBase Accession No. MI0025511, SEQ ID NO: 17 5) is known.

[0139] As used herein, "hsa-miR-4736 gene" or "hsa-miR-4 The term "miR-4736" refers to the hsa-miR-4736 gene (miR Base Accession No. MIMAT0019862) and other species of Homo sapiens The hsa-miR-4736 gene is a member of the Per sson H et al., 2011, Cancer Res., Vol. 71, p78-86 hsa-miR-4736 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure. Session No. MI0017373, SEQ ID NO: 176) is known.

[0140] As used herein, "hsa-miR-5100 gene" or "hsa-miR-5 The term "miR-5100" refers to the hsa-miR-5100 gene (miR-5100) set forth in SEQ ID NO: 54. Base Accession No. MIMAT0022259) and other species of Homo sapiens The hsa-miR-5100 gene is a member of the Tan family of miR-5100 genes. Don M et al., 2012, Oral Dis., Vol. 18, p127-131 Furthermore, "hsa-miR-5100" can be obtained by the method described above. The miRBase Accession No. 100012666644444444 has a hairpin-like structure as a target protein. The sequence number of the nucleotide sequence ...

[0141] As used herein, "hsa-miR-6724-5p gene" or "hsa-mi The term "miR-6724-5p" refers to hsa-miR-6724-5p as set forth in SEQ ID NO: 55. 5p gene (miRBase Accession No. MIMAT0025856) hsa-miR-672 and other species homologs or orthologs. The 4-5p gene is described in Li Y et al., 2012, Gene., Vol. 497, pp. 330-335. The miR-6724-5p gene can be obtained by the method described in " has a hairpin-like structure as its precursor "hsa-mir-6724 (miRB)" The enzyme (Accession No. MI0022559, SEQ ID NO: 178) is known There are.

[0142] As used herein, "hsa-miR-7107-5p gene" or "hsa-mi The term "miR-7107-5p" refers to hsa-miR-7107- 5p gene (miRBase Accession No. MIMAT0028111) and other species homologs or orthologs. The 7-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-7107-5p has a hairpin-like structure as its precursor, "hsa-mi r-7107" (miRBase Accession No. MI0022958, Column number 179) is known.

[0143] As used herein, "hsa-miR-6726-5p gene" or "hsa-mi The term "miR-6726-5p" refers to hsa-miR-6726-5p as set forth in SEQ ID NO: 57. 5p gene (miRBase Accession No. MIMAT0027353) hsa-miR-672 and other species homologs or orthologs. The 6-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6726-5p has a hairpin-like structure as its precursor, "hsa-mi r-6726" (miRBase Accession No. MI0022571, Column number 180) is known.

[0144] As used herein, "hsa-miR-3185 gene" or "hsa-miR-3 The term "miR-3185" refers to the hsa-miR-3185 gene (miR-3185) set forth in SEQ ID NO: 58. Base Accession No. MIMAT0015065) and other species of Homo sapiens The hsa-miR-3185 gene is a member of the Sta rk MS et al., 2010, PLoS One., Vol. 5, e9685 Furthermore, "hsa-miR-3185" can be obtained as a precursor of hsa-miR-3185. The miRBase Accession No. 100001266666 (hsa-mir-3185) has an apin-like structure. n No. MI0014227, SEQ ID NO: 181) is known.

[0145] As used herein, "hsa-miR-4638-5p gene" or "hsa-mi The term "miR-4638-5p" refers to hsa-miR-4638-5p as set forth in SEQ ID NO: 59. 5p gene (miRBase Accession No. MIMAT0019695) hsa-miR-463 and other species homologs or orthologs. The 8-5p gene is Persson H et al., 2011, Cancer Res., 71 The hsa-miR can be obtained by the method described in Vol. -4638-5p is a precursor of hsa-mir-46, which has a hairpin-like structure. 38" (miRBase Accession No. MI0017265, SEQ ID NO: 1 82) is known.

[0146] As used herein, "hsa-miR-1273g-3p gene" or "hsa-m The term "hsa-miR-1273g-3p" refers to hsa-miR-1273g-3p as set forth in SEQ ID NO: 60. 3g-3p gene (miRBase Accession No. MIMAT00227 42) and other species homologs or orthologs. The 1273g-3p gene is described in Reshmi G et al., 2011, Genomics., 9 It can be obtained by the method described in Vol. 7, pp. 333-340. miR-1273g-3p has a hairpin-like structure as its precursor, hsa-mi r-1273g” (miRBase Accession No. MI0018003, SEQ ID NO: 183) is known.

[0147] As used herein, "hsa-miR-6778-5p gene" or "hsa-mi The term "miR-6778-5p" refers to hsa-miR-6778- 5p gene (miRBase Accession No. MIMAT0027456) hsa-miR-677 and other species homologs or orthologs. The 8-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6778-5p has a hairpin-like structure as its precursor, "hsa-mi r-6778" (miRBase Accession No. MI0022623, Column number 184) is known.

[0148] As used herein, "hsa-miR-328-5p gene" or "hsa-miR The term "miR-328-5p" refers to the hsa-miR-328-5p gene set forth in SEQ ID NO: 62. gene (miRBase Accession No. MIMAT0026486) and its It also includes homologs or orthologs from other species. Genes are described in Kim J et al., 2004, Proc Natl Acad Sci, 101 It can be obtained by the method described in Vol. 1, pp. 360-365. iR-328-5p is a precursor of hsa-mir-3, which has a hairpin-like structure. 28" (miRBase Accession No. MI0000804, SEQ ID NO: 1 85) is known.

[0149] As used herein, "hsa-miR-3679-3p gene" or "hsa-mi The term "miR-3679-3p" refers to hsa-miR-3679-3p as set forth in SEQ ID NO: 63. 3p gene (miRBase Accession No. MIMAT0018105) hsa-miR-367 and other species homologs or orthologs. The 9-3p gene is Creighton CJ et al., 2010, PLoS One., 5 The miR-hsa gene can be obtained by the method described in Vol. 3679-3p is a precursor of hsa-mir-367, which has a hairpin-like structure. 9" (miRBase Accession No. MI0016080, SEQ ID NO: 18 6) is known.

[0150] As used herein, "hsa-miR-1228-3p gene" or "hsa-mi The term "miR-1228-3p" refers to hsa-miR-1228-3p as set forth in SEQ ID NO: 64. 3p gene (miRBase Accession No. MIMAT0005583) hsa-miR-122 and other species homologs or orthologs. The 8-3p gene is described in Berezikov E et al., 2007, Mol Cell., 28 It can be obtained by the method described in Vol. 1, pp. 328-336. iR-1228-3p is a precursor of the hairpin-like structure known as hsa-mir- 1228" (miRBase Accession No. MI0006318, sequence no. No. 187) is known.

[0151] As used herein, "hsa-miR-6779-5p gene" or "hsa-mi The term "miR-6779-5p" refers to hsa-miR-6779-5p as set forth in SEQ ID NO: 65. 5p gene (miRBase Accession No. MIMAT0027458) hsa-miR-677 and other species homologs or orthologs. The 9-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6779-5p has a hairpin-like structure as its precursor, "hsa-mi r-6779” (miRBase Accession No. MI0022624, Column number 188) is known.

[0152] As used herein, "hsa-miR-4723-5p gene" or "hsa-mi The term "miR-4723-5p" refers to hsa-miR-4723-5p as set forth in SEQ ID NO: 66. 5p gene (miRBase Accession No. MIMAT0019838) hsa-miR-472 and other species homologs or orthologs. The 3-5p genes are described in Persson H et al., 2011, Cancer Res., 71 The hsa-miR can be obtained by the method described in Vol. -4723-5p is a precursor of hsa-mir-47, which has a hairpin-like structure. 23" (miRBase Accession No. MI0017359, SEQ ID NO: 1 89) is known.

[0153] As used herein, "hsa-miR-6850-5p gene" or "hsa-mi The term "miR-6850-5p" refers to hsa-miR-6850-5p as set forth in SEQ ID NO: 67. 5p gene (miRBase Accession No. MIMAT0027600) hsa-miR-685 and other species homologs or orthologs. The 0-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6850-5p has a hairpin-like structure as its precursor, "hsa-mi r-6850" (miRBase Accession No. MI0022696, Column number 190) is known.

[0154] As used herein, "hsa-miR-760 gene" or "hsa-miR-76 The term "miR-760" refers to the hsa-miR-760 gene (miRBas) set forth in SEQ ID NO: 68. e Accession No. MIMAT0004957) and homologs in other species The hsa-miR-760 gene is a member of the Berezik ov E et al., 2006, Genome Res., Vol. 16, p1289-1298 hsa-miR-760 can be obtained by the method described in the literature. The miRBase Accelerator, "hsa-mir-760" (miRBase Accelerator), has a hairpin-like structure. Session No. MI0005567, SEQ ID NO: 191) is known.

[0155] As used herein, "hsa-miR-7704 gene" or "hsa-miR-7 The term "miR-7704" refers to the hsa-miR-7704 gene (miR Base Accession No. MIMAT0030019) and other species of Homo sapiens The hsa-miR-7704 gene is a member of the Swa minathan S et al., 2013, Biochem Biophys Res Co It can be obtained by the method described in Mmun., Vol. 434, pp. 228-234. In addition, "hsa-miR-7704" has a hairpin-like structure as its precursor, "hs a-mir-7704” (miRBase Accession No. MI00252 40, SEQ ID NO: 192) is known.

[0156] As used herein, "hsa-miR-8072 gene" or "hsa-miR-8 The term "miR-8072" refers to the hsa-miR-8072 gene (miR-8072) set forth in SEQ ID NO: 70. Base Accession No. MIMAT0030999) and other species of Homo sapiens The hsa-miR-8072 gene is a member of the Wan The method described in g HJ et al., 2013, Shock., Vol. 39, p. 480-487 hsa-miR-8072 can be obtained as a precursor of hsa-miR-8072. The miRBase Accession No. 1244444 (hsa-mir-8072) has an apin-like structure. n No. MI0025908, sequence number 193) is known.

[0157] As used herein, "hsa-miR-4486 gene" or "hsa-miR-4 The term "miR-4486" refers to the hsa-miR-4486 gene (miR Base Accession No. MIMAT0019020) and other species of Homo sapiens The hsa-miR-4486 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4486 can be obtained by the method described above. The miRBase Accession No. 100002606 (hsa-mir-4486) has a hairpin-like structure. ion No. MI0016847, SEQ ID NO: 194) is known.

[0158] As used herein, "hsa-miR-1913 gene" or "hsa-miR-1 The term "miR-1913" refers to the hsa-miR-1913 gene (miR Base Accession No. MIMAT0007888) and other species of Homo sapiens The hsa-miR-1913 gene is a member of the Bar M et al., 2008, Stem Cells., Vol. 26, p2496-2505 Furthermore, "hsa-miR-1913" can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-1913" ( Session No. MI0008334, SEQ ID NO: 195) is known.

[0159] As used herein, "hsa-miR-4656 gene" or "hsa-miR-4 The term "miR-4656" refers to the hsa-miR-4656 gene (miR Base Accession No. MIMAT0019723) and other species of Homo sapiens The hsa-miR-4656 gene is a member of the Per sson H et al., 2011, Cancer Res., Vol. 71, p78-86 Furthermore, "hsa-miR-4656" can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4656" ( Session No. MI0017284, SEQ ID NO: 196) is known.

[0160] As used herein, "hsa-miR-1260b gene" or "hsa-miR- The term "miR-1260b" refers to the hsa-miR-1260b gene ( miRBase Accession No. MIMAT0015041) and other organisms The hsa-miR-1260b gene is a member of the family of miR-1260b. , Stark MS et al., 2010, PLoS One., Vol. 5, e9685 hsa-miR-1260b can be obtained by the method described above. The miRBase Ac Accession No. MI0014197, SEQ ID NO: 197) is known.

[0161] As used herein, "hsa-miR-7106-5p gene" or "hsa-mi The term "hsa-miR-7106-5p" refers to hsa-miR-7106- 5p gene (miRBase Accession No. MIMAT0028109) and other species homologs or orthologs. The 6-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-7106-5p has a hairpin-like structure as its precursor, "hsa-mi r-7106" (miRBase Accession No. MI0022957, Column number 198) is known.

[0162] As used herein, "hsa-miR-6889-5p gene" or "hsa-mi The term "miR-6889-5p" refers to hsa-miR-6889-5p as set forth in SEQ ID NO: 76. 5p gene (miRBase Accession No. MIMAT0027678) hsa-miR-688 and other species homologs or orthologs. The 9-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6889-5p has a hairpin-like structure as its precursor, "hsa-mi r-6889" (miRBase Accession No. MI0022736, Column number 199) is known.

[0163] As used herein, "hsa-miR-6780b-5p gene" or "hsa-m The term "hsa-miR-6780b-5p" refers to hsa-miR-6780b-5p as set forth in SEQ ID NO: 77. 0b-5p gene (miRBase Accession No. MIMAT00275 72) and other species homologs or orthologs. The 6780b-5p gene is from Ladewig E et al., 2012, Genome Res ., Vol. 22, pp. 1634-1645. "hsa-miR-6780b-5p" is a precursor of "hsa-miR-6780b-5p" which has a hairpin-like structure. sa-mir-6780b” (miRBase Accession No. MI002 2681, SEQ ID NO: 200) is known.

[0164] As used herein, "hsa-miR-6090 gene" or "hsa-miR-6 The term "miR-6090" refers to the hsa-miR-6090 gene (miR-6090) set forth in SEQ ID NO: 78. Base Accession No. MIMAT0023715) and other species of Homo sapiens The hsa-miR-6090 gene is a member of the Yoo JK et al., 2013, Arch Pharm Res. 36, pp. 353-358 hsa-miR-6090 can be obtained by the method described in the The precursor of "hsa-mir-6090" (miRBase A Accession No. MI0020367, SEQ ID NO: 201) is known.

[0165] As used herein, "hsa-miR-4534 gene" or "hsa-miR-4 The term "miR-4534" refers to the hsa-miR-4534 gene (miR Base Accession No. MIMAT0019073) and other species of Homo sapiens The hsa-miR-4534 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4534 can be obtained by the method described above. The miRBase Accession No. 10000266666 (hsa-mir-4534) has a hairpin-like structure. ion No. MI0016901, SEQ ID NO: 202) is known.

[0166] As used herein, "hsa-miR-4449 gene" or "hsa-miR-4 The term "miR-4449" refers to the hsa-miR-4449 gene (miR Base Accession No. MIMAT0018968) and other species of Homo sapiens The hsa-miR-4449 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4449 can be obtained by the method described above. The miRBase Accession No. 1006266666 (hsa-mir-4449) forms a hairpin-like structure. ion No. MI0016792, SEQ ID NO: 203) is known.

[0167] As used herein, "hsa-miR-5195-3p gene" or "hsa-mi The term "miR-5195-3p" refers to hsa-miR-5195-3p as set forth in SEQ ID NO: 81. 3p gene (miRBase Accession No. MIMAT0021127) hsa-miR-519 and other species homologs or orthologs. The 5-3p gene is Schotte D et al., 2011, Leukemia., Vol. 25, It can be obtained by the method described on pages 1389-1399. iR-5195-3p is a precursor of the hairpin-like structure known as hsa-mir- 5195" (miRBase Accession No. MI0018174, sequence no. No. 204) is known.

[0168] As used herein, "hsa-miR-1202 gene" or "hsa-miR-1 The term "miR-1202" refers to the hsa-miR-1202 gene (miR-1202) set forth in SEQ ID NO: 82. Base Accession No. MIMAT0005865) and other species of Homo sapiens The hsa-miR-1202 gene is a member of the Mar ton S et al., 2008, Leukemia., Vol. 22, p. 330-338 Furthermore, "hsa-miR-1202" can be obtained by the method described above. The miRBase Accession No. 1202 (hsa-mir-1202) has a hairpin-like structure. The sequence number of the nucleotide sequence ...

[0169] As used herein, "hsa-miR-4467 gene" or "hsa-miR-4 The term "miR-4467" refers to the hsa-miR-4467 gene (miR Base Accession No. MIMAT0018994) and other species of Homo sapiens The hsa-miR-4467 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4467 can be obtained by the method described above. The miRBase Accession No. 1000020 ... ion No. MI0016818, SEQ ID NO: 206) is known.

[0170] As used herein, "hsa-miR-6515-3p gene" or "hsa-mi The term "miR-6515-3p" refers to hsa-miR-6515-3p as set forth in SEQ ID NO: 84. 3p gene (miRBase Accession No. MIMAT0025487) hsa-miR-651 and other species homologs or orthologs. The 5-3p gene is described in Joyce CE et al., 2011, Hum Mol Genet. It can be obtained by the method described in Vol. 20, pp. 4025-4040. sa-miR-6515-3p has a hairpin-like structure as its precursor, hsa- mir-6515” (miRBase Accession No. MI0022227 , SEQ ID NO: 207) is known.

[0171] As used herein, "hsa-miR-4281 gene" or "hsa-miR-4 The term "miR-4281" refers to the hsa-miR-4281 gene (miR Base Accession No. MIMAT0016907) and other species of Homo sapiens The hsa-miR-4281 gene is a member of the Gof f By the method described in LA et al., 2009, PLoS One., Vol. 4, e7192 In addition, "hsa-miR-4281" can be obtained by The pin-like structure of "hsa-mir-4281" (miRBase Accession No. No. MI0015885, SEQ ID NO: 208) is known.

[0172] As used herein, "hsa-miR-4505 gene" or "hsa-miR-4 The term "miR-4505" refers to the hsa-miR-4505 gene (miR Base Accession No. MIMAT0019041) and other species of Homo sapiens The hsa-miR-4505 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4505 can be obtained by the method described above. The miRBase Accession No. 10000266666 (hsa-mir-4505) has a hairpin-like structure. ion No. MI0016868, SEQ ID NO: 209) is known.

[0173] As used herein, "hsa-miR-4484 gene" or "hsa-miR-4 The term "miR-4484" refers to the hsa-miR-4484 gene (miR Base Accession No. MIMAT0019018) and other species of Homo sapiens The hsa-miR-4484 gene is a member of the Jim a) DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4484 can be obtained by the method described above. The miRBase Accession No. 100002666666 (hsa-mir-4484) forms a hairpin-like structure. Ion No. MI0016845, SEQ ID NO: 210) is known.

[0174] As used herein, "hsa-miR-6805-3p gene" or "hsa-mi The term "hsa-miR-6805-3p" refers to hsa-miR-6805-3p as set forth in SEQ ID NO: 88. 3p gene (miRBase Accession No. MIMAT0027511) hsa-miR-680 and other species homologs or orthologs. The 5-3p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6805-3p has a hairpin-like structure as its precursor, "hsa-mi r-6805” (miRBase Accession No. MI0022650, Column number 211) is known.

[0175] As used herein, "hsa-miR-3135b gene" or "hsa-miR- The term "miR-3135b" refers to the hsa-miR-3135b gene ( miRBase Accession No. MIMAT0018985) and other organisms The hsa-miR-3135b gene is a member of the family of miR-3135b. , Jima DD et al., 2010, Blood., Vol. 116, e118-e127 Furthermore, "hsa-miR-3135b" can be obtained by the method described above. The precursor of "hsa-mir-3135b" (miRBase Accession No. MI0016809, SEQ ID NO: 212) is known.

[0176] As used herein, "hsa-miR-3162-5p gene" or "hsa-mi The term "hsa-miR-3162-5p" refers to hsa-miR-3162-5p as set forth in SEQ ID NO: 90. 5p gene (miRBase Accession No. MIMAT0015036) hsa-miR-316 and other species homologs or orthologs. The 2-5p gene is Stark MS et al., 2010, PLoS One., Vol. 5, e9 685. -5p" has a hairpin-like structure as its precursor, "hsa-mir-3162" (m iRBase Accession No. MI0014192, sequence number 213) It is being done.

[0177] As used herein, "hsa-miR-6768-5p gene" or "hsa-mi The term "miR-6768-5p" refers to hsa-miR-6768-5p as set forth in SEQ ID NO: 91. 5p gene (miRBase Accession No. MIMAT0027436) hsa-miR-676 and other species homologs or orthologs. The 8-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6768-5p has a hairpin-like structure as its precursor, "hsa-mi r-6768" (miRBase Accession No. MI0022613, Column number 214) is known.

[0178] As used herein, "hsa-miR-6721-5p gene" or "hsa-mi The term "miR-6721-5p" refers to hsa-miR-6721-5p as set forth in SEQ ID NO: 92. 5p gene (miRBase Accession No. MIMAT0025852) hsa-miR-672 and other species homologs or orthologs. The 1-5p gene is described in Li Y et al., 2012, Gene., Vol. 497, pp. 330-335. The miR-6721-5p gene can be obtained by the method described in " has a hairpin-like structure as its precursor, "hsa-mir-6721" (miRB The enzyme (Accession No. MI0022556, SEQ ID NO: 215) is known There are.

[0179] As used herein, "hsa-miR-1227-5p gene" or "hsa-mi The term "miR-1227-5p" refers to hsa-miR-1227-5p as set forth in SEQ ID NO: 93. 5p gene (miRBase Accession No. MIMAT0022941) hsa-miR-122 and other species homologs or orthologs. The 7-5p gene is described in Berezikov E et al., 2007, Mol Cell., 28 It can be obtained by the method described in Vol. 1, pp. 328-336. iR-1227-5p is a precursor of the hairpin-like structure known as hsa-mir- 1227" (miRBase Accession No. MI0006316, sequence no. No. 216) is known.

[0180] As used herein, "hsa-miR-6722-3p gene" or "hsa-mi The term "miR-6722-3p" refers to hsa-miR-6722-3p as set forth in SEQ ID NO: 94. 3p gene (miRBase Accession No. MIMAT0025854) hsa-miR-672 and other species homologs or orthologs. The 2-3p gene is described in Li Y et al., 2012, Gene., Vol. 497, pp. 330-335. The miR-6722-3p gene can be obtained by the method described in " has a hairpin-like structure as its precursor, "hsa-mir-6722" (miRB The enzyme (Accession No. MI0022557, SEQ ID NO: 217) is known There are.

[0181] As used herein, "hsa-miR-4286 gene" or "hsa-miR-4 The term "miR-4286" refers to the hsa-miR-4286 gene (miR Base Accession No. MIMAT0016916) and other species of Homo sapiens The hsa-miR-4286 gene is a member of the Gof f By the method described in LA et al., 2009, PLoS One., Vol. 4, e7192 In addition, "hsa-miR-4286" can be obtained by The pin-like structure of "hsa-mir-4286" (miRBase Accession No. No. MI0015894, SEQ ID NO: 218) is known.

[0182] As used herein, "hsa-miR-4746-3p gene" or "hsa-mi The term "miR-4746-3p" refers to hsa-miR-4746-3p as set forth in SEQ ID NO: 96. 3p gene (miRBase Accession No. MIMAT0019881) hsa-miR-474 and other species homologs or orthologs. The 6-3p gene is Persson H et al., 2011, Cancer Res., 71 The hsa-miR can be obtained by the method described in Vol. -4746-3p is a precursor of hsa-mir-47, which has a hairpin-like structure. 46" (miRBase Accession No. MI0017385, SEQ ID NO: 2 19) is known.

[0183] As used herein, "hsa-miR-6727-5p gene" or "hsa-mi The term "miR-6727-5p" refers to hsa-miR-6727-5p as set forth in SEQ ID NO: 97. 5p gene (miRBase Accession No. MIMAT0027355) hsa-miR-672 and other species homologs or orthologs. The 7-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6727-5p has a hairpin-like structure as its precursor, "hsa-mi r-6727” (miRBase Accession No. MI0022572, Column number 220) is known.

[0184] As used herein, "hsa-miR-6816-5p gene" or "hsa-mi The term "miR-6816-5p" refers to hsa-miR-6816-5p as set forth in SEQ ID NO: 98. 5p gene (miRBase Accession No. MIMAT0027532) hsa-miR-681 and other species homologs or orthologs. The 6-5p gene is Ladewig E et al., 2012, Genome Res., 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6816-5p has a hairpin-like structure as its precursor, "hsa-mi r-6816" (miRBase Accession No. MI0022661, Column number 221) is known.

[0185] As used herein, "hsa-miR-4741 gene" or "hsa-miR-4 The term "miR-4741" refers to the hsa-miR-4741 gene (miR Base Accession No. MIMAT0019871) and other species of Homo sapiens The hsa-miR-4741 gene is a member of the Per sson H et al., 2011, Cancer Res., Vol. 71, p78-86 hsa-miR-4741 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4741" ( Session No. MI0017379, SEQ ID NO: 222) is known.

[0186] As used herein, "hsa-miR-4508 gene" or "hsa-miR-4 The term "miR-4508" refers to the hsa-miR-4508 gene (miR-4508) set forth in SEQ ID NO: 100. RBase Accession No. MIMAT0019045) and other species The hsa-miR-4508 gene is a homologue or ortholog. Ma DD et al., 2010, Blood., Vol. 116, e118-e127 Furthermore, "hsa-miR-4508" can be obtained by the method described above. The miRBase Accession No. 1006266666, which forms a hairpin-like structure, is sion No. MI0016872, SEQ ID NO: 223) is known.

[0187] As used herein, "hsa-miR-940 gene" or "hsa-miR-94 The term "miR-940" refers to the hsa-miR-940 gene (miRBa se Accession No. MIMAT0004983) and other species homologs The hsa-miR-940 gene is a gene encoding miR-940. et al., 2007, A Cancer Res., Vol. 67, p. 6031-6043 hsa-miR-940 can be obtained by the method described above. The miRBase Accession No. 100001266664 ... sion No. MI0005762, SEQ ID NO: 224) is known.

[0188] As used herein, "hsa-miR-4327 gene" or "hsa-miR-4 The term "miR-4327" refers to the hsa-miR-4327 gene (miR-4327) set forth in SEQ ID NO: 102. RBase Accession No. MIMAT0016889) and other species The hsa-miR-4327 gene is a homologue or ortholog. The method described in ff LA et al., 2009, PLoS One., Vol. 4, e7192 hsa-miR-4327 can be obtained by The apin-like structure of "hsa-mir-4327" (miRBase Accession No. 1001001001001) n No. MI0015867, sequence number 225) is known.

[0189] As used herein, "hsa-miR-4665-3p gene" or "hsa-mi The term "miR-4665-3p" refers to hsa-miR-4665 as set forth in SEQ ID NO: 103. -3p gene (miRBase Accession No. MIMAT0019740 ) and other species homologs or orthologs. The 65-3p gene is described in Persson H et al., 2011, Cancer Res., 7 It can be obtained by the method described in Vol. 1, pp. 78-86. R-4665-3p is a precursor of hsa-mir-4, which has a hairpin-like structure. 665" (miRBase Accession No. MI0017295, SEQ ID NO: 159) is known.

[0190] As used herein, "hsa-miR-718 gene" or "hsa-miR-71 The term "miR-718" refers to the hsa-miR-718 gene (miRBa se Accession No. MIMAT0012735) and other species homologs The hsa-miR-718 gene is a member of the Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39 hsa-miR-718 can be obtained by the method described above. The miRBase Accession No. 1006266666, which has a hairpin-like structure, is a missense mutation in the miR-1 gene. ion No. MI0012489, SEQ ID NO: 226) is known.

[0191] As used herein, "hsa-miR-125a-3p gene" or "hsa-mi The term "miR-125a-3p" refers to hsa-miR-125a as set forth in SEQ ID NO: 105. -3p gene (miRBase Accession No. MIMAT0004602 ) and other species homologs or orthologs. The 5a-3p gene is described in Lagos-Quintana M et al., 2002, Curr B It can be obtained by the method described in Iol., Vol. 12, pp. 735-739. "hsa-miR-125a-3p" is a precursor of "hsa-miR-125a-3p" which has a hairpin-like structure. sa-mir-125a” (miRBase Accession No. MI0000 469, SEQ ID NO: 227) is known.

[0192] As used herein, "hsa-miR-204-3p gene" or "hsa-miR The term "miR-204-3p" refers to hsa-miR-204-3p as set forth in SEQ ID NO: 106. Gene (miRBase Accession No. MIMAT0022693) and This includes homologs or orthologs of hsa-miR-204-3 in other species. The p gene is described in Lim LP et al., 2003, Science., Vol. 299, p. 1540. hsa-miR-204-3p can be obtained by the method described in , and its precursor, "hsa-mir-204" (miRBase Accession No. MI0000284, SEQ ID NO: 228) is known.

[0193] As used herein, "hsa-miR-1469 gene" or "hsa-miR-1 The term "miR-1469" refers to the hsa-miR-1469 gene (miR-1469) set forth in SEQ ID NO: 107. RBase Accession No. MIMAT0007347) and other species The hsa-miR-1469 gene is a homologue or ortholog. Waji H et al., 2008, BMC Genomics, Vol. 9, p. 157 hsa-miR-1469 can be obtained by the method described above. The miRBase Accession No. 1469 (hsa-mir-1469) forms a hairpin-like structure. sion No. MI0007074, SEQ ID NO: 229) is known.

[0194] As used herein, "hsa-miR-575 gene" or "hsa-miR-57 The term "miR-575" refers to the hsa-miR-575 gene (miRBa se Accession No. MIMAT0003240) and other species homologs The hsa-miR-575 gene is a member of the Cumming s JM, 2006, Proc Natl Acad Sci, vol. 103, p3687 The miR-57 can be obtained by the method described in US Pat. 5” has a hairpin-like structure as its precursor, “hsa-mir-575” (miRB The enzyme (Accession No. MI0003582, SEQ ID NO: 230) is known There are.

[0195] As used herein, "hsa-miR-150-3p gene" or "hsa-miR The term "miR-150-3p" refers to hsa-miR-150-3p set forth in SEQ ID NO: 109. Gene (miRBase Accession No. MIMAT0004610) and This includes homologs or orthologs of hsa-miR-150-3 in other species. The p gene is described in Lagos-Quintana M et al., 2002, Curr Biol. It can be obtained by the method described in Vol. 12, pp. 735-739. a-miR-150-3p is a precursor of hsa-miR, which has a hairpin-like structure. r-150" (miRBase Accession No. MI0000479, sequence Number 231) is known.

[0196] As used herein, "hsa-miR-423-5p gene" or "hsa-miR The term "miR-423-5p" refers to hsa-miR-423-5p as set forth in SEQ ID NO: 110. Gene (miRBase Accession No. MIMAT0004748) and This includes homologs or orthologs of hsa-miR-423-5 in other species. The p gene was identified by Kasashima K et al., 2004, Biochem Biophys Res Commun., vol. 322, pp. 403-410 Furthermore, "hsa-miR-423-5p" has a hairpin The miRBase Accession No. .MI0001445, sequence number 232) is known.

[0197] As used herein, "hsa-miR-564 gene" or "hsa-miR-56 The term "miR-564" refers to the hsa-miR-564 gene (miRBa se Accession No. MIMAT0003228) and other species homologs The hsa-miR-564 gene is a member of the Cumming s JM, 2006, Proc Natl Acad Sci, vol. 103, p3687 The miR-56 can be obtained by the method described in US Pat. 4” has a hairpin-like structure as its precursor, “hsa-mir-564” (miRB4). The enzyme (Accession No. MI0003570, SEQ ID NO: 233) is known There are.

[0198] As used herein, "hsa-miR-3188 gene" or "hsa-miR-3 The term "miR-3188" refers to the hsa-miR-3188 gene (miR-3188) set forth in SEQ ID NO: 112. RBase Accession No. MIMAT0015070) and other species The hsa-miR-3188 gene is a homologue or ortholog of the St The method described in ark MS et al., 2010, PLoS One., Vol. 5, e9685 Furthermore, "hsa-miR-3188" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-3188" (miRBase Accession No. on No. MI0014232, SEQ ID NO: 234) is known.

[0199] As used herein, "hsa-miR-1246 gene" or "hsa-miR-1 The term "miR-1246" refers to the hsa-miR-1246 gene (miR-1246) set forth in SEQ ID NO: 113. RBase Accession No. MIMAT0005898) and other species The hsa-miR-1246 gene is a homologue or ortholog. Rin RD et al., 2008, Genome Res., Vol. 18, p. 610-621 hsa-miR-1246 can be obtained by the method described in the The precursor of "hsa-mir-1246" (miRBase A Accession No. MI0006381, SEQ ID NO: 235) is known.

[0200] As used herein, "hsa-miR-602 gene" or "hsa-miR-60 The term "miR-602" refers to the hsa-miR-602 gene (miRBa se Accession No. MIMAT0003270) and other species homologs The hsa-miR-602 gene is a member of the Cumming s JM, 2006, Proc Natl Acad Sci, vol. 103, p3687 The miR-60 can be obtained by the method described in US Pat. 2” has a hairpin-like structure as its precursor, “hsa-mir-602” (miRB The enzyme (Accession No. MI0003615, SEQ ID NO: 236) is known There are.

[0201] As used herein, "hsa-miR-1290 gene" or "hsa-miR-1 The term "miR-1290" refers to the hsa-miR-1290 gene (miR-1290) set forth in SEQ ID NO: 115. RBase Accession No. MIMAT0005880) and other species The hsa-miR-1290 gene is a homologue or ortholog. Rin RD et al., 2008, Genome Res., Vol. 18, p. 610-621 hsa-miR-1290 can be obtained by the method described in the The precursor of "hsa-mir-1290" (miRBase A Accession No. MI0006352, SEQ ID NO: 237) is known.

[0202] As used herein, "hsa-miR-16-5p gene" or "hsa-miR- The term "miR-16-5p" refers to the hsa-miR-16-5p gene set forth in SEQ ID NO: 116. (miRBase Accession No. MIMAT0000069) and other Species homologs or orthologs are included. hsa-miR-16-5p gene Lagos-Quintana M et al., 2002, Curr Biol., vol. 12 It can be obtained by the method described in the "Hsa-mi R-16-5p is a precursor of hsa-mir-16-, which has a hairpin-like structure. 1, hsa-mir-16-2” (miRBase Accession No. MI 0000070, MI0000115, SEQ ID NOs: 238, 239) are known.

[0203] As used herein, "hsa-miR-451a gene" or "hsa-miR-4 The term "miR-451a" refers to the hsa-miR-451a gene (mi RBase Accession No. MIMAT0001631) and other species The hsa-miR-451a gene is a homologue or ortholog. Tuvia Y et al., 2005, Nucleic Acids Res., Vol. 33, p. 2 The hsa-miR can be obtained by the method described in -451a” has a hairpin-like structure as its precursor “hsa-mir-451a” (miRBase Accession No. MI0001729, SEQ ID NO: 240) is known.

[0204] As used herein, "hsa-miR-24-3p gene" or "hsa-miR- The term "miR-24-3p" refers to the hsa-miR-24-3p gene set forth in SEQ ID NO: 118. (miRBase Accession No. MIMAT0000080) and other Species homologs or orthologs are included. hsa-miR-24-3p gene Lagos-Quintana M et al., 2001, Science., Vol. 294, The miR gene can be obtained by the method described on pages 853-858. -24-3p is a precursor of hsa-mir-24-1, which has a hairpin-like structure. , hsa-mir-24-2” (miRBase Accession No. MI00 00080, MI0000081, SEQ ID NOs: 241, 242) are known.

[0205] As used herein, "hsa-miR-187-5p gene" or "hsa-miR The term "miR-187-5p" refers to hsa-miR-187-5p as set forth in SEQ ID NO: 119. Gene (miRBase Accession No. MIMAT0004561) and This includes homologs or orthologs of hsa-miR-187-5 in other species. The p gene is described in Lim LP et al., 2003, Science., Vol. 299, p. 1540. hsa-miR-187-5p can be obtained by the method described in , and its precursor, "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 243) is known.

[0206] As used herein, "hsa-miR-1908-5p gene" or "hsa-mi The term "miR-1908-5p" refers to hsa-miR-1908 as set forth in SEQ ID NO: 120. -5p gene (miRBase Accession No. MIMAT0007881 ) and other species homologs or orthologs. The 08-5p gene is described in Bar M et al., 2008, Stem Cells., Vol. 26, p. 2496-2505. R-1908-5p is a precursor of hsa-mir-1, which has a hairpin-like structure. 908" (miRBase Accession No. MI0008329, SEQ ID NO: 244) is known.

[0207] As used herein, "hsa-miR-371a-5p gene" or "hsa-mi The term "miR-371a-5p" refers to hsa-miR-371a set forth in SEQ ID NO: 121. -5p gene (miRBase Accession No. MIMAT0004687 ) and other species homologs or orthologs. The 1a-5p gene is described in Suh MR et al., 2004, Dev Biol., vol. 270, p. The "hsa-miR- 371a-5p is a precursor of hsa-mir-371, which has a hairpin-like structure. a" (miRBase Accession No. MI0000779, SEQ ID NO: 24 5) is known.

[0208] As used herein, "hsa-miR-550a-5p gene" or "hsa-mi The term "miR-550a-5p" refers to hsa-miR-550a set forth in SEQ ID NO: 122. -5p gene (miRBase Accession No. MIMAT0004800 ) and other species homologs or orthologs. The 0a-5p gene is described in Cummins JM, 2006, Proc Natl Aca d Sci, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-550a-5p" has a hairpin-like structure as its precursor. Take "hsa-mir-550a-1, hsa-mir-550a-2" (miRBas e Accession No. MI0003600, MI0003601, SEQ ID NO: 2 46, 247) are known.

[0209] As used herein, "hsa-miR-4417 gene" or "hsa-miR-4 The term "miR-4417" refers to the hsa-miR-4417 gene (miR-4417) set forth in SEQ ID NO: 349. RBase Accession No. MIMAT0018929) and other species The hsa-miR-4417 gene is a homologue or ortholog of the Ji Ma DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-4417 can be obtained by the method described above. The miRBase Accession No. 1000020 ... ion No. MI0016753, SEQ ID NO: 384) is known.

[0210] As used herein, "hsa-miR-4707-5p gene" or "hsa-mi The term "miR-4707-5p" refers to hsa-miR-4707 as set forth in SEQ ID NO: 350. -5p gene (miRBase Accession No. MIMAT0019807 ) and other species homologs or orthologs. The 07-5p gene is described in Persson H et al., 2011, Cancer Res, 71 The hsa-miR can be obtained by the method described in Vol. -4707-5p is a precursor of hsa-mir-47, which has a hairpin-like structure. 07" (miRBase Accession No. MI0017340, SEQ ID NO: 3 85) is known.

[0211] As used herein, "hsa-miR-7847-3p gene" or "hsa-mi The term "miR-7847-3p" refers to hsa-miR-7847 as set forth in SEQ ID NO: 351. -3p gene (miRBase Accession No. MIMAT0030422 ) and other species homologs or orthologs. The 47-3p gene is Ple H et al., 2012, PLoS One, Vol. 7, e5074 6. Also, "hsa-miR-7847-3 p” has a hairpin-like structure as its precursor “hsa-mir-7847” (miR Base Accession No. MI0025517, SEQ ID NO: 386) is known are.

[0212] As used herein, "hsa-miR-2861 gene" or "hsa-miR-2 The term "miR-2861" refers to the hsa-miR-2861 gene (miR-2861) set forth in SEQ ID NO: 352. RBase Accession No. MIMAT0013802) and other species The hsa-miR-2861 gene is a homologue or ortholog. H et al., 2009, J Clin Invest, Vol. 119, p3666-3677 hsa-miR-2861 can be obtained by the method described in The precursor of the hairpin-like structure "hsa-mir-2861" (miRBase Accession No. MI0013006, SEQ ID NO: 387) is known.

[0213] As used herein, "hsa-miR-4513 gene" or "hsa-miR-4 The term "miR-4513" refers to the hsa-miR-4513 gene (miR-4513) set forth in SEQ ID NO: 353. RBase Accession No. MIMAT0019050) and other species The hsa-miR-4513 gene is a homologue or ortholog. Ma DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-4513 can be obtained by the method described above. The miRBase Accession No. 134446644 (hsa-mir-4513) forms a hairpin-like structure. ion No. MI0016879, SEQ ID NO: 388) is known.

[0214] As used herein, "hsa-miR-7111-5p gene" or "hsa-mi The term "miR-7111-5p" refers to hsa-miR-7111 set forth in SEQ ID NO: 354. -5p gene (miRBase Accession No. MIMAT0028119 ) and other species homologs or orthologs. The 11-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-7111-5p has a hairpin-like structure as its precursor, "hsa-mi r-7111" (miRBase Accession No. MI0022962, Column number 389) is known.

[0215] As used herein, "hsa-miR-6777-5p gene" or "hsa-mi The term "miR-6777-5p" refers to hsa-miR-6777 set forth in SEQ ID NO: 355. -5p gene (miRBase Accession No. MIMAT0027454 ) and other species homologs or orthologs. The 77-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6777-5p has a hairpin-like structure as its precursor, "hsa-mi r-6777” (miRBase Accession No. MI0022622, Column number 390) is known.

[0216] As used herein, "hsa-miR-7113-3p gene" or "hsa-mi The term "miR-7113-3p" refers to hsa-miR-7113 as set forth in SEQ ID NO: 356. -3p gene (miRBase Accession No. MIMAT0028124 ) and other species homologs or orthologs. The 13-3p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-7113-3p has a hairpin-like structure as its precursor, "hsa-mi r-7113" (miRBase Accession No. MI0022964, Column number 391) is known.

[0217] As used herein, "hsa-miR-4648 gene" or "hsa-miR-4 The term "miR-4648" refers to the hsa-miR-4648 gene (miR-4648) set forth in SEQ ID NO: 357. RBase Accession No. MIMAT0019710) and other species The hsa-miR-4648 gene is a homologue or ortholog of the rsson H et al., 2011, Cancer Res, Vol. 71, p78-86 hsa-miR-4648 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4648" ( Session No. MI0017275, SEQ ID NO: 392) is known.

[0218] As used herein, "hsa-miR-3184-5p gene" or "hsa-mi The term "miR-3184-5p" refers to hsa-miR-3184 set forth in SEQ ID NO: 358. -5p gene (miRBase Accession No. MIMAT0015064 ) and other species homologs or orthologs. The 84-5p gene is described in Stark MS et al., 2010, PLoS One, Vol. 5, e9 685. -5p" has a hairpin-like structure as its precursor, "hsa-mir-3184" (m iRBase Accession No. MI0014226, sequence number 393) It is being done.

[0219] As used herein, "hsa-miR-4271 gene" or "hsa-miR-4 The term "miR-4271" refers to the hsa-miR-4271 gene (miR-4271) set forth in SEQ ID NO: 359. RBase Accession No. MIMAT0016901) and other species The hsa-miR-4271 gene is a homologue or ortholog. According to the method described in ff LA et al., 2009, PLoS One, Vol. 4, e7192 In addition, "hsa-miR-4271" can be obtained by The pin-like structure of "hsa-mir-4271" (miRBase Accession No. No. MI0015879, SEQ ID NO: 394) is known.

[0220] As used herein, "hsa-miR-6791-5p gene" or "hsa-mi The term "miR-6791-5p" refers to hsa-miR-6791 set forth in SEQ ID NO: 360. -5p gene (miRBase Accession No. MIMAT0027482 ) and other species homologs or orthologs. The 91-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6791-5p has a hairpin-like structure as its precursor, "hsa-mi r-6791" (miRBase Accession No. MI0022636, Column number 395) is known.

[0221] As used herein, "hsa-miR-642a-3p gene" or "hsa-mi The term "miR-642a-3p" refers to hsa-miR-642a set forth in SEQ ID NO: 361. -3p gene (miRBase Accession No. MIMAT0020924 ) and other species homologs or orthologs. The 2a-3p genes are described in Cummins JM et al., 2006, Proc Natl Ac ad Sci USA, Vol. 103, p3687-3692, Landgraf P et al., 2 007, Cell, Vol. 129, p1401-1414, Zaragosi LE et al., 2 obtained by the method described in Genome Biol, Vol. 12, R64, etc. In addition, "hsa-miR-642a-3p" is a precursor of hairpin The miRBase Accession No. 1000012666644444 has a phosphodiesterase-like structure, "hsa-mir-642a" (miRBase Accession No. 10000126666644444). No. MI0003657, SEQ ID NO: 396) is known.

[0222] As used herein, "hsa-miR-7108-5p gene" or "hsa-mi The term "miR-7108-5p" refers to hsa-miR-7108 as set forth in SEQ ID NO: 362. -5p gene (miRBase Accession No. MIMAT0028113 ) and other species homologs or orthologs. The 08-5p gene is described in Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-7108-5p has a hairpin-like structure as its precursor, "hsa-mi r-7108” (miRBase Accession No. MI0022959, Column number 397) is known.

[0223] As used herein, "hsa-miR-128-1-5p gene" or "hsa-m The term "miR-128-1-5p" refers to hsa-miR-128-1-5p as set forth in SEQ ID NO: 363. 8-1-5p gene (miRBase Accession No. MIMAT0026 477) and other species homologs or orthologs. The -128-1-5p gene is a member of the Lagos-Quintana M et al., 2002, Cu rr Biol, Vol. 12, p735-739, Kasashima K et al., 2004, Biochem Biophys Res Commun, volume 322, p403-410 , Landgraf P et al., 2007, Cell, Vol. 129, p1401-1414, Meunier J et al., 2013, Genome Res, Vol. 23, p34-45, The "hsa-miR-128-1- 5p" has a hairpin-like structure as its precursor, "hsa-mir-128-1" (m iRBase Accession No. MI0000447, sequence number 398) It is being done.

[0224] As used herein, "hsa-miR-5196-5p gene" or "hsa-mi The term "miR-5196-5p" refers to hsa-miR-5196 as set forth in SEQ ID NO: 364. -5p gene (miRBase Accession No. MIMAT0021128 ) and other species homologs or orthologs. The 96-5p gene is Schotte D et al., 2011, Leukemia, Vol. 25, It can be obtained by the method described on pages 1389-1399. iR-5196-5p is a precursor of the hairpin-like structure known as hsa-mir- 5196" (miRBase Accession No. MI0018175, sequence no. No. 399) is known.

[0225] As used herein, "hsa-miR-3178 gene" or "hsa-miR-3 The term "miR-3178" refers to the hsa-miR-3178 gene (miR-3178) set forth in SEQ ID NO: 365. RBase Accession No. MIMAT0015055) and other species The hsa-miR-3178 gene is a homologue or ortholog of the St The method described in ark MS et al., 2010, PLoS One, Vol. 5, e9685 hsa-miR-3178 can be obtained by The miRBase Accession No. hsa-mir-3178 (hsa-mir-3178) has an apin-like structure. n No. MI0014212, SEQ ID NO: 400) is known.

[0226] As used herein, "hsa-miR-3656 gene" or "hsa-miR-3 The term "miR-3656" refers to the hsa-miR-3656 gene (miR-3656) set forth in SEQ ID NO: 366. RBase Accession No. MIMAT0018076) and other species The hsa-miR-3656 gene is a homologue or ortholog of the Me Iri E et al., 2010, Nucleic Acids Res, Vol. 38, p. 6234 The miR-36 can be obtained by the method described in US Pat. No. 6,246,624. 56" has a hairpin-like structure as its precursor, "hsa-mir-3656" (mi RBase Accession No. MI0016056, sequence number 401) It is being done.

[0227] As used herein, "hsa-miR-92a-2-5p gene" or "hsa-m The term "miR-92a-2-5p" refers to hsa-miR-92a-2-5p as set forth in SEQ ID NO: 367. a-2-5p gene (miRBase Accession No. MIMAT0004 508) and other species homologs or orthologs. The -92a-2-5p gene is described in Mourelatos Z et al., 2002, Genes Dev, vol. 16, p720-728, Dostie J et al., 2003, RNA, vol. 9, p180-186, Houbaviy HB et al., 2003, Dev Cell, 5 volumes, p351-358, Suh MR et al., 2004, Dev Biol, Vol. 270, p48 8-498, Kasashima K et al., 2004, Biochem Biophys Res Commun, vol. 322, p403-410, Fu H et al., 2005, FE BS Lett, vol. 579, p3849-3854, Landgraf P et al., 2007 Cell, vol. 129, p1401-1414, Lui WO et al., 2007, Can Cer Res, Vol. 67, pp. 6031-6043, etc. In addition, "hsa-miR-92a-2-5p" can be synthesized as a hairpin miR-92a precursor. The miRBase Accession No. 100001266644 (hsa-mir-92a-2) has a similar structure to the miR-10001266644 (hsa-mir-92a-2) (miRBase Accession No. 100001266444). No. MI0000094, SEQ ID NO: 402) is known.

[0228] As used herein, "hsa-miR-6769b-5p gene" or "hsa-m The term "miR-6769b-5p" refers to hsa-miR-6769b-5p as set forth in SEQ ID NO: 368. 69b-5p gene (miRBase Accession No. MIMAT0027 620) and other species homologs or orthologs. The -6769b-5p gene is from Ladewig E et al., 2012, Genome Re It can be obtained by the method described in Vol. 22, pp. 1634-1645. "hsa-miR-6769b-5p" is a precursor of "hsa-miR-6769b-5p" which has a hairpin-like structure. sa-mir-6769b” (miRBase Accession No. MI002 2706, SEQ ID NO: 403) is known.

[0229] As used herein, "hsa-miR-4689 gene" or "hsa-miR-4 The term "miR-4689" refers to the hsa-miR-4689 gene (miR-4689) set forth in SEQ ID NO: 369. RBase Accession No. MIMAT0019778) and other species The hsa-miR-4689 gene is a homologue or ortholog of the rsson H et al., 2011, Cancer Res, Vol. 71, p78-86 hsa-miR-4689 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4689" ( Session No. MI0017322, SEQ ID NO: 404) is known.

[0230] As used herein, "hsa-miR-6076 gene" or "hsa-miR-6 The term "miR-6076" refers to the hsa-miR-6076 gene (miR-6076) set forth in SEQ ID NO: 370. RBase Accession No. MIMAT0023701) and other species The hsa-miR-6076 gene is a homologue or ortholog of the Vo Described in Ellenkle C et al., 2012, RNA, Vol. 18, p. 472-484 hsa-miR-6076 can be obtained by the method described above. The miRBase Accession No. 1000026444444444 forms a hairpin-like structure. sion No. MI0020353, SEQ ID NO: 405) is known.

[0231] As used herein, "hsa-miR-92b-5p gene" or "hsa-miR The term "miR-92b-5p" refers to hsa-miR-92b-5p as set forth in SEQ ID NO: 371. Gene (miRBase Accession No. MIMAT0004792) and This includes homologs or orthologs of hsa-miR-92b-5 from other species. The p gene is described in Cummins JM et al., 2006, Proc Natl Acad S ci USA, vol. 103, p3687-3692, Landgraf P et al., 2007 , Cell, Vol. 129, p1401-1414, Lui WO et al., 2007, Canc It can be obtained by the method described in, for example, J. Org. Res., Vol. 67, pp. 6031-6043. In addition, "hsa-miR-92b-5p" has a hairpin-like structure as its precursor. The miRBase Accession No. 0003560, SEQ ID NO: 406) is known.

[0232] As used herein, "hsa-miR-6774-5p gene" or "hsa-mi The term "miR-6774-5p" refers to hsa-miR-6774 set forth in SEQ ID NO: 372. -5p gene (miRBase Accession No. MIMAT0027448 ) and other species homologs or orthologs. The 74-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6774-5p has a hairpin-like structure as its precursor, "hsa-mi r-6774” (miRBase Accession No. MI0022619, Column number 407) is known.

[0233] As used herein, "hsa-miR-486-3p gene" or "hsa-miR The term "miR-486-3p" refers to hsa-miR-486-3p set forth in SEQ ID NO: 373. Gene (miRBase Accession No. MIMAT0004762) and This includes homologs or orthologs of hsa-miR-486-3 in other species. The p gene is described in Fu H et al., 2005, FEBS Lett, Vol. 579, p3849-3. 854, Landgraf P et al., 2007, Cell, Vol. 129, p1401-14 14. Meunier J et al., 2013, Genome Res, Vol. 23, p34-4 5, etc. 3p" has a hairpin-like structure as its precursor, "hsa-mir-486, hsa- mir-486-2” (miRBase Accession No. MI000247 0, MI0023622, SEQ ID NOs: 408, 409) are known.

[0234] As used herein, "hsa-miR-6806-5p gene" or "hsa-mi The term "miR-6806-5p" refers to hsa-miR-6806 set forth in SEQ ID NO: 374. -5p gene (miRBase Accession No. MIMAT0027512 ) and other species homologs or orthologs. The 06-5p gene is described in Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6806-5p has a hairpin-like structure as its precursor, "hsa-mi r-6806" (miRBase Accession No. MI0022651, Column number 410) is known.

[0235] As used herein, "hsa-miR-6842-5p gene" or "hsa-mi The term "miR-6842-5p" refers to hsa-miR-6842 set forth in SEQ ID NO: 375. -5p gene (miRBase Accession No. MIMAT0027586 ) and other species homologs or orthologs. The 42-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6842-5p has a hairpin-like structure as its precursor, "hsa-mi r-6842” (miRBase Accession No. MI0022688, Column number 411) is known.

[0236] As used herein, "hsa-miR-6716-5p gene" or "hsa-mi The term "miR-6716-5p" refers to hsa-miR-6716 set forth in SEQ ID NO: 376. -5p gene (miRBase Accession No. MIMAT0025844 ) and other species homologs or orthologs. The 16-5p gene is described in Li Y et al., 2012, Gene, Vol. 497, p330-335. The miR-6716-5p gene can be obtained by the method described in " has a hairpin-like structure as its precursor "hsa-mir-6716" (miRB The enzyme (Accession No. MI0022550, SEQ ID NO: 412) is known There are.

[0237] As used herein, "hsa-miR-557 gene" or "hsa-miR-55 The term "miR-557" refers to the hsa-miR-557 gene (miRBa se Accession No. MIMAT0003221) and other species homologs The hsa-miR-557 gene is a member of the Cumming s JM et al., 2006, Proc Natl Acad Sci USA, 103 It can be obtained by the method described in Vol. 1, pp. 3687-3692. -miR-557 has a hairpin-like structure as its precursor, hsa-mir-55 7" (miRBase Accession No. MI0003563, SEQ ID NO: 41 3) is known.

[0238] As used herein, "hsa-miR-4673 gene" or "hsa-miR-4 The term "miR-4673" refers to the hsa-miR-4673 gene (miR-4673) set forth in SEQ ID NO: 378. RBase Accession No. MIMAT0019755) and other species The hsa-miR-4673 gene is a homologue or ortholog of the rsson H et al., 2011, Cancer Res, Vol. 71, p78-86 hsa-miR-4673 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4673" ( Session No. MI0017304, SEQ ID NO: 414) is known.

[0239] As used herein, "hsa-miR-4674 gene" or "hsa-miR-4 The term "miR-4674" refers to the hsa-miR-4674 gene (miR-4674) set forth in SEQ ID NO: 379. RBase Accession No. MIMAT0019756) and other species The hsa-miR-4674 gene is a homologue or ortholog of the rsson H et al., 2011, Cancer Res, Vol. 71, p78-86 hsa-miR-4674 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4674" ( Session No. MI0017305, SEQ ID NO: 415) is known.

[0240] As used herein, "hsa-miR-4442 gene" or "hsa-miR-4 The term "miR-4442" refers to the hsa-miR-4442 gene (miR-4442) set forth in SEQ ID NO: 380. RBase Accession No. MIMAT0018960) and other species The hsa-miR-4442 gene is a homologue or ortholog of the Ji Ma DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-4442 can be obtained by the method described above. The miRBase Accession No. 1001166666, which has a hairpin-like structure, is a missense mutation called "hsa-mir-4442" (miRBase Accession No. 100116666666). ion No. MI0016785, SEQ ID NO: 416) is known.

[0241] As used herein, "hsa-miR-1915-3p gene" or "hsa-mi The term "miR-1915-3p" refers to hsa-miR-1915 as set forth in SEQ ID NO: 381. -3p gene (miRBase Accession No. MIMAT0007892 ) and other species homologs or orthologs. The 15-3p gene is described in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2 The hsa-miR can be obtained by the method described in JP 496-2505. -1915-3p is a precursor of hsa-mir-19, which has a hairpin-like structure. 15" (miRBase Accession No. MI0008336, SEQ ID NO: 4 17) is known.

[0242] As used herein, "hsa-miR-4687-3p gene" or "hsa-mi The term "miR-4687-3p" refers to hsa-miR-4687 set forth in SEQ ID NO: 382. -3p gene (miRBase Accession No. MIMAT0019775 ) and other species homologs or orthologs. The 87-3p gene is described in Persson H et al., 2011, Cancer Res, 71 The hsa-miR can be obtained by the method described in Vol. -4687-3p is a precursor of hsa-mir-46, which has a hairpin-like structure. 87" (miRBase Accession No. MI0017319, SEQ ID NO: 4 18) is known.

[0243] As used herein, "hsa-miR-92b-3p gene" or "hsa-miR The term "miR-92b-3p" refers to hsa-miR-92b-3p set forth in SEQ ID NO: 383. Gene (miRBase Accession No. MIMAT0003218) and This includes homologs or orthologs of hsa-miR-92b-3 in other species. The p gene is described in Cummins JM et al., 2006, Proc Natl Acad S ci USA, Vol. 103, p3687-3692, Landgraf P et al., 200 7, Cell, Vol. 129, p1401-1414, Lui WO et al., 2007, Ca It can be obtained by the method described in Cancer Res, Vol. 67, pp. 6031-6043. In addition, "hsa-miR-92b-3p" has a hairpin-like structure as its precursor. The miRBase Accession No. 0003560, SEQ ID NO: 419) is known.

[0244] As used herein, "hsa-miR-1203 gene" or "hsa-miR-1 The term "miR-1203" refers to the hsa-miR-1203 gene (miR-1203) set forth in SEQ ID NO: 464. RBase Accession No. MIMAT0005866) and other species The hsa-miR-1203 gene is a homologue or ortholog. rton S et al., 2008, Leukemia., Vol. 22, p. 330-338 hsa-miR-1203 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-1203" ( Session No. MI0006335, SEQ ID NO: 467) is known.

[0245] As used herein, "hsa-miR-663b gene" or "hsa-miR-6 The term "miR-663b" refers to the hsa-miR-663b gene (mi RBase Accession No. MIMAT0005867) and other species The hsa-miR-663b gene is a homologue or ortholog of the Ta Kada S et al., 2008, Leukemia., Vol. 22, p. 1274-1278 hsa-miR-663b can be obtained by the method described in the The precursor "hsa-mir-663b" (miRBase A Accession No. MI0006336, SEQ ID NO: 475) is known.

[0246] As used herein, "hsa-miR-4258 gene" or "hsa-miR-4 The term "miR-4258" refers to the hsa-miR-4258 gene (miR-4258) set forth in SEQ ID NO: 466. RBase Accession No. MIMAT0016879) and other species The hsa-miR-4258 gene is a homologue of the Go The method described in ff LA et al., 2009, PLoS One., Vol. 4, e7192 hsa-miR-4258 can be obtained by The miRBase Accession No. hsa-mir-4258 (hsa-mir-4258) has an apin-like structure. n No. MI0015857, sequence number 476) is known.

[0247] As used herein, "hsa-miR-4649-5p gene" or "hsa-mi The term "miR-4649-5p" refers to hsa-miR-4649 set forth in SEQ ID NO: 467. -5p gene (miRBase Accession No. MIMAT0019711 ) and other species homologs or orthologs. The 49-5p gene is described in Persson H et al., 2011, Cancer Res., 7 It can be obtained by the method described in Vol. 1, pp. 78-86. R-4649-5p is a precursor of hsa-mir-4, which has a hairpin-like structure. 649" (miRBase Accession No. MI0017276, SEQ ID NO: 477) is known.

[0248] As used herein, "hsa-miR-4516 gene" or "hsa-miR-4 The term "miR-4516" refers to the hsa-miR-4516 gene (miR-4516) set forth in SEQ ID NO: 468. RBase Accession No. MIMAT0019053) and other species The hsa-miR-4516 gene is a homologue or ortholog. Ma DD et al., 2010, Blood., Vol. 116, e118-e127 Furthermore, "hsa-miR-4516" can be obtained by the method The miRBase Accession No. 1000012644444444 forms a hairpin-like structure. sion No. MI0016882, SEQ ID NO: 478) is known.

[0249] As used herein, "hsa-miR-3619-3p gene" or "hsa-mi The term "miR-3619-3p" refers to hsa-miR-3619 set forth in SEQ ID NO: 469. -3p gene (miRBase Accession No. MIMAT0019219 ) and other species homologs or orthologs. The 19-3p gene is described in Witten D et al., 2010, BMC Biol., Vol. 8, p. 58. Also, "hsa-miR-3619- 3p" has a hairpin-like structure as its precursor "hsa-mir-3619" (mi RBase Accession No. MI0016009, sequence number 479) It is being done.

[0250] As used herein, "hsa-miR-6826-5p gene" or "hsa-mi The term "miR-6826-5p" refers to hsa-miR-6826 set forth in SEQ ID NO: 470. -5p gene (miRBase Accession No. MIMAT0027552 ) and other species homologs or orthologs. The 26-5p gene is described in Ladewig E et al., 2012, Genome Res., 2 It can be obtained by the method described in Vol. 2, pp. 1634-1645. a-miR-6826-5p has a hairpin-like structure as its precursor, hsa-m ir-6826” (miRBase Accession No. MI0022671, SEQ ID NO: 480) is known.

[0251] As used herein, "hsa-miR-6757-5p gene" or "hsa-mi The term "miR-6757-5p" refers to hsa-miR-6757 as set forth in SEQ ID NO: 471. -5p gene (miRBase Accession No. MIMAT0027414 ) and other species homologs or orthologs. The 57-5p gene is described in Ladewig E et al., 2012, Genome Res., 2 It can be obtained by the method described in Vol. 2, pp. 1634-1645. a-miR-6757-5p has a hairpin-like structure as its precursor, hsa-m ir-6757” (miRBase Accession No. MI0022602, SEQ ID NO: 481) is known.

[0252] As used herein, "hsa-miR-3131 gene" or "hsa-miR-3 The term "miR-3131" refers to the hsa-miR-3131 gene (miR-3131) set forth in SEQ ID NO: 472. RBase Accession No. MIMAT0014996) and other species The hsa-miR-3131 gene is a homologue or ortholog of the St The method described in ark MS et al., 2010, PLoS One., Vol. 5, e9685 In addition, "hsa-miR-3131" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-3131" (miRBase Accession No. on No. MI0014151, SEQ ID NO: 482) is known.

[0253] As used herein, "hsa-miR-1343-3p gene" or "hsa-mi The term "miR-1343-3p" refers to hsa-miR-1343 as set forth in SEQ ID NO: 473. -3p gene (miRBase Accession No. MIMAT0019776 ) and other species homologs or orthologs. The 43-3p gene is described in Persson H et al., 2011, Cancer Res., 7 It can be obtained by the method described in Vol. 1, pp. 78-86. R-1343-3p is a precursor of hsa-mir-1, which has a hairpin-like structure. 343" (miRBase Accession No. MI0017320, SEQ ID NO: 483) is known.

[0254] As used herein, "hsa-miR-6775-5p gene" or "hsa-mi The term "miR-6775-5p" refers to hsa-miR-6775 set forth in SEQ ID NO: 492. -5p gene (miRBase Accession No. MIMAT0027450 ) and other species homologs or orthologs. The 75-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6775-5p has a hairpin-like structure as its precursor, "hsa-mi r-6775" (miRBase Accession No. MI0022620, Column number 495) is known.

[0255] As used herein, "hsa-miR-6813-5p gene" or "hsa-mi The term "miR-6813-5p" refers to hsa-miR-6813 set forth in SEQ ID NO: 493. -5p gene (miRBase Accession No. MIMAT0027526 ) and other species homologs or orthologs. The 13-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6813-5p has a hairpin-like structure as its precursor, "hsa-mi r-6813" (miRBase Accession No. MI0022658, Column number 496) is known.

[0256] As used herein, "hsa-miR-3940-5p gene" or "hsa-mi The term "miR-3940-5p" refers to hsa-miR-3940 set forth in SEQ ID NO: 494. -5p gene (miRBase Accession No. MIMAT0019229 ) and other species homologs or orthologs. The 40-5p gene is Liao JY et al., 2010, PLoS One, Vol. 5, e10 563. Also, "hsa-miR-3940" can be obtained by the method described in -5p" has a hairpin-like structure as its precursor, "hsa-mir-3940" (m iRBase Accession No. MI0016597, sequence number 497) It is being done.

[0257] Furthermore, mature miRNAs are derived from RNA precursors with hairpin-like structures. When excised as iRNA, one to several bases before and after the sequence may be excised shorter or longer. In some cases, base substitutions occur, resulting in mutants, which are called isomiRs (Mori n RD. et al., 2008, Genome Res., Vol. 18, pp. 610-621) In miRBase Release 20, SEQ ID NOs: 1 to 122, 349 to 383, and 4 In addition to the base sequences represented by either 64-473 or 492-494, there are numerous isoforms SEQ ID NOs: 248-348, 420-463, 484-491 and 498, referred to as miRs Variants and fragments of the base sequence represented by any of the sequences from 1 to 499 are also shown. The antibody also includes the antibodies of SEQ ID NOs: 1 to 122, 349 to 383, 464 to 473, and 492 to 494. The miRNA of the present invention can be obtained as a miRNA having a base sequence represented by any one of the following: SEQ ID NOs: 6, 10, 12, 13, 15, 18, 19, 23, 30, 33, 34, 41, 4 3, 46, 48, 51, 55, 59, 60, 62, 63, 64, 66, 68, 71, 74 , 80, 83, 86, 87, 89, 90, 92, 95, 99, 100, 101, 105, 106, 109, 110, 112, 113, 115, 116, 117, 118, 119, 121, 349, 350, 352, 353, 357, 359, 361, 363, 364, 365, 366, 367, 369, 371, 373, 376, 378, 379, 380, The base sequences represented by 381, 382, 383, 465, 468, 472, 473, and 492 or a variant of a polynucleotide consisting of a base sequence in which u is replaced by t For example, the longest variant registered in miRBase Release 20 and SEQ ID NOs: 248, 250, 251, 253, 255, 257, 259, 262, 265, 267, 268, 272, 275, 277, 278, 279, 282, 285, 287, 289, 291, 292, 294, 296, 298, 300, 302, 305, 306, 307, 309, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 334, 336, 337, 339, 341, 342, 344, 346, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 484, 486, 488, 490, and 498. In addition, the polynucleotides of the present invention are represented by SEQ ID NOs: 6, 10, and 11. , 12, 13, 15, 18, 19, 23, 30, 33, 34, 41, 43, 46, 48, 51, 55, 59, 60, 62, 63, 64, 66, 68, 71, 74, 80, 83, 8 6, 87, 89, 90, 92, 95, 99, 100, 101, 105, 106, 109, 110, 112, 113, 115, 116, 117, 118, 119, 121, 349, 350, 352, 353, 357, 359, 361, 363, 364, 365, 366, 367, 369, 371, 373, 376, 378, 379, 380, 381, 382, The base sequences represented by 383, 465, 468, 472, 473 and 492 or the bases Among variants of a polynucleotide consisting of a base sequence in which u is t, for example, The shortest variants registered in miRBase Release 20 are Sequence numbers 249, 252, 254, 256, 258, 260, 261, 263, and 264 , 266, 269, 270, 271, 273, 274, 276, 280, 281, 283 , 284, 286, 288, 290, 293, 295, 297, 299, 301, 303 , 304, 308, 311, 313, 315, 317, 319, 321, 323, 325 , 327, 329, 331, 333, 335, 338, 340, 343, 345, 347 , 348, 421, 423, 425, 427, 429, 431, 433, 435, 437 , 439, 441, 443, 445, 447, 449, 451, 453, 455, 457 , 459, 461, 463, 485, 487, 489, 491, and 499 In addition to these variants and fragments, miRB polynucleotides are also included. Sequence numbers 6, 10, 12, 13, 15, 18, 19, 23, and 30, registered in ase, 33, 34, 41, 43, 46, 48, 51, 55, 59, 60, 62, 63, 64, 6 6, 68, 71, 74, 80, 83, 86, 87, 89, 90, 92, 95, 99, 10 0, 101, 105, 106, 109, 110, 112, 113, 115, 116, 11 7, 118, 119, 121, 349, 350, 352, 353, 357, 359, 36 1, 363, 364, 365, 366, 367, 369, 371, 373, 376, 37 8, 379, 380, 381, 382, 383, 465, 468, 472, 473 and 4 92 polynucleotides that are isomiRs. a base represented by any one of 122, 349 to 383, 464 to 473, and 492 to 494 Examples of polynucleotides containing the sequences include the precursors SEQ ID NOs: 123 to 24. Polynuclear groups represented by any of 7, 384-419, 474-483, and 495-497 Examples include cleotide.

[0258] Names of genes represented by SEQ ID NOs: 1 to 499 and miRBase Accession Numbers The registration numbers are listed in Table 1.

[0259] As used herein, the term "capable of specifically binding" refers to the nucleic acid probe or probe used in the present invention. This means that the primer binds to a specific target nucleic acid and is substantially incapable of binding to other nucleic acids. .

[0260] [Table 1]

[0261] TIFF2025118849000003.tif252113

[0262] TIFF2025118849000004.tif252115

[0263] TIFF2025118849000005.tif250117

[0264] TIFF2025118849000006.tif252111

[0265] TIFF2025118849000007.tif252115

[0266] TIFF2025118849000008.tif254117

[0267] TIFF2025118849000009.tif254121

[0268] TIFF2025118849000010.tif253116

[0269] TIFF2025118849000011.tif253117

[0270] TIFF2025118849000012.tif249110

[0271] TIFF2025118849000013.tif44117

[0272] This specification is based on Japanese Patent Applications Nos. 2014-113523 and 2014-185730, from which the present application claims priority. It encompasses the contents described in the specification and / or drawings. [Effects of the Invention]

[0273] The present invention makes it possible to detect pancreatic cancer easily and with high accuracy.

[0274] For example, several miRNAs can be expressed in the blood, serum, and / or plasma of patients, which can be collected minimally invasively. Using the measured amount as an index, it is possible to easily detect whether a patient has pancreatic cancer. [Brief explanation of the drawings]

[0275] [Figure 1] This figure shows the relationship between the base sequences of hsa-miR-4665-5p, represented by sequence number 36, which is generated from its precursor hsa-mir-4665, represented by sequence number 159, and hsa-miR-4665-3p, represented by sequence number 103. [Figure 2]Left: The vertical axis shows the measured expression levels of hsa-miR-6893-5p (SEQ ID NO: 1) in healthy individuals (100 individuals) and pancreatic cancer patients (67 individuals) selected as the training sample group. The horizontal line in the figure indicates the threshold (8.02) for discriminating between the two groups, optimized by Fisher's discriminant analysis. Right: The vertical axis shows the measured expression levels of hsa-miR-6893-5p (SEQ ID NO: 1) in healthy individuals (50 individuals) and pancreatic cancer patients (33 individuals) selected as the test sample group. The horizontal line in the figure indicates the threshold (8.02) for discriminating between the two groups, set in the training sample group. [Figure 3] Left: The horizontal axis shows the measured expression levels of hsa-miR-6893-5p (SEQ ID NO: 1) and the vertical axis shows the measured expression levels of hsa-miR-6075 (SEQ ID NO: 2) for healthy individuals (100 individuals, circles) and pancreatic cancer patients (67 individuals, triangles) selected as the training sample group. The line in the figure represents the discriminant function (0 = 1.74x + y + 5.14) optimized by Fisher's discriminant analysis to discriminate between the two groups. Right: The horizontal axis shows the measured expression levels of hsa-miR-6893-5p (SEQ ID NO: 1) and the vertical axis shows the measured expression levels of hsa-miR-6075 (SEQ ID NO: 2) for healthy individuals (50 individuals, circles) and pancreatic cancer patients (33 individuals, triangles) selected as the test sample group. The line in the figure represents the threshold (0 = 1.74x + y + 5.14) for discriminating between the two groups, set in the training sample group. [Figure 4]Upper figure: hsa-miR-6075 (SEQ ID NO: 2), hsa-miR-6836-3p (SEQ ID NO: 7), hsa-miR-6799-5p (SEQ ID NO: 9), hsa-miR-125a-3p (SEQ ID NO: 10), and hsa-miR-125b-3p (SEQ ID NO: 11) of 67 pancreatic cancer patients, 93 healthy subjects, 35 colorectal cancer patients, 37 gastric cancer patients, 32 esophageal cancer patients, 38 liver cancer patients, and 13 patients with benign pancreatic and biliary diseases selected as the learning sample group. A discriminant equation was created using Fisher's discriminant analysis from the expression level measurements of miR-6075 (SEQ ID NO: 105) (1.64 × hsa-miR-6075 + 1.02 × hsa-miR-6836-3p - 0.35 × hsa-miR-6799-5p - 0.06 × hsa-miR-125a-3p - 20.67), and the discriminant score obtained from the discriminant equation is plotted on the vertical axis and the sample group on the horizontal axis. The dotted line in the figure indicates the discriminant boundary for distinguishing between the two groups, where the discriminant score is 0. The figure below shows the expression level measurements of hsa-miR-6075 (SEQ ID NO: 2), hsa-miR-6799-5p (SEQ ID NO: 9), hsa-miR-125a-3p (SEQ ID NO: 105), and hsa-miR-6836-3p (SEQ ID NO: 7) for the test sample group: 33 pancreatic cancer patients, 57 healthy subjects, 15 colorectal cancer patients, 13 gastric cancer patients, 18 esophageal cancer patients, 12 liver cancer patients, and 8 patients with benign pancreatic and biliary diseases. The discriminant score obtained from the discriminant equation created for the training sample group is plotted on the vertical axis, and the sample group is plotted on the horizontal axis. The dotted line in the figure indicates the discriminant boundary for distinguishing between the two groups, where the discriminant score is 0. DETAILED DESCRIPTION OF THE INVENTION

[0276] The present invention will be explained in more detail below. 1. Target nucleic acids for pancreatic cancer The nucleic acid probe or primer for detecting pancreatic cancer defined above of the present invention is used to detect pancreatic cancer. as a pancreatic cancer marker for detecting the presence and / or absence of pancreatic cancer or pancreatic cancer cells; The main target nucleic acids of miR-6893-5p, miR-6075, hsa-miR-6820-5p, hsa-miR-4294, hsa-miR-672 9-5p、hsa-miR-4476、hsa-miR-6836-3p、hsa-mi R-6765-3p、hsa-miR-6799-5p、hsa-miR-4530、h sa-miR-7641、hsa-miR-4454、hsa-miR-615-5p、 hsa-miR-8073, hsa-miR-663a, hsa-miR-4634, h sa-miR-4450、hsa-miR-4792、hsa-miR-665、hsa -miR-7975、hsa-miR-7109-5p、hsa-miR-6789-5 p、hsa-miR-4497、hsa-miR-6877-5p、hsa-miR-6 880-5p、hsa-miR-7977、hsa-miR-4734、hsa-miR -6821-5p、hsa-miR-8089、hsa-miR-5585-3p、hs a-miR-6085、hsa-miR-6845-5p、hsa-miR-4651、 hsa-miR-4433-3p, hsa-miR-1231, hsa-miR-466 5-5p、hsa-miR-7114-5p、hsa-miR-1238-5p、hsa -miR-8069、hsa-miR-4732-5p、hsa-miR-619-5p 、hsa-miR-3622a-5p、hsa-miR-1260a、hsa-miR- 6741-5p、hsa-miR-6781-5p、hsa-miR-6125、hsa -miR-6805-5p、hsa-miR-6132、hsa-miR-6872-3 p、hsa-miR-6875-5p、hsa-miR-1908-3p、hsa-mi R-4433b-3p、hsa-miR-4736、hsa-miR-5100、hsa -miR-6724-5p、hsa-miR-7107-5p、hsa-miR-672 6-5p、hsa-miR-3185、hsa-miR-4638-5p、hsa-mi R-1273g-3p、hsa-miR-6778-5p、hsa-miR-328-5 p、hsa-miR-3679-3p、hsa-miR-1228-3p、hsa-mi R-6779-5p、hsa-miR-4723-5p、hsa-miR-6850-5 p、hsa-miR-760、hsa-miR-7704、hsa-miR-8072、 hsa-miR-4486、hsa-miR-1913、hsa-miR-4656、h sa-miR-1260b、hsa-miR-7106-5p、hsa-miR-688 9-5p、hsa-miR-6780b-5p、hsa-miR-6090、hsa-m iR-4534、hsa-miR-4449、hsa-miR-5195-3p、hsa -miR-1202、hsa-miR-4467、hsa-miR-6515-3p、h sa-miR-4281, hsa-miR-4505, hsa-miR-4484, hs a-miR-6805-3p、hsa-miR-3135b、hsa-miR-3162 -5p、hsa-miR-6768-5p、hsa-miR-6721-5p、hsa- miR-1227-5p、hsa-miR-6722-3p、hsa-miR-4286 hsa-miR-4746-3p, hsa-miR-6727-5p, hsa-miR -6816-5p、hsa-miR-4741、hsa-miR-4508、hsa-m iR-940、hsa-miR-4327、hsa-miR-4665-3p、hsa- miR-718, hsa-miR-1203, hsa-miR-663b, hsa-mi R-4258, hsa-miR-4649-5p, hsa-miR-4516, hsa- miR-3619-3p, hsa-miR-6826-5p, hsa-miR-6757 -5p, hsa-miR-3131, hsa-miR-1343-3p, hsa-miR -6775-5p, hsa-miR-6813-5p and hsa-miR-3940-5 p. Furthermore, these Other pancreatic cancer markers that can be combined with miRNAs, namely, hsa-m iR-125a-3p, hsa-miR-204-3p, hsa-miR-1469, h sa-miR-575, hsa-miR-150-3p, hsa-miR-423-5p , hsa-miR-564, hsa-miR-3188, hsa-miR-1246, h sa-miR-602, hsa-miR-1290, hsa-miR-16-5p, hs a-miR-451a, hsa-miR-24-3p, hsa-miR-187-5p, hsa-miR-1908-5p, hsa-miR-371a-5p and hsa-miR -550a-5p, and at least one or more miRNA target nucleic acids selected from the group consisting of Furthermore, it can be preferably used in combination with these miRNAs. Other pancreatic cancer markers that can be used include hsa-miR-4417, hsa-miR-4 707-5p, hsa-miR-7847-3p, hsa-miR-2861, hsa- miR-4513, hsa-miR-7111-5p, hsa-miR-6777-5p , hsa-miR-7113-3p, hsa-miR-4648, hsa-miR-31 84-5p, hsa-miR-4271, hsa-miR-6791-5p, hsa-m iR-642a-3p, hsa-miR-7108-5p, hsa-miR-128-1 -5p, hsa-miR-5196-5p, hsa-miR-3178, hsa-miR -3656, hsa-miR-92a-2-5p, hsa-miR-6769b-5p, hsa-miR-4689, hsa-miR-6076, hsa-miR-92b-5p , hsa-miR-6774-5p, hsa-miR-486-3p, hsa-miR- 6806-5p, hsa-miR-6842-5p, hsa-miR-6716-5p, hsa-miR-557, hsa-miR-4673, hsa-miR-4674, hs a-miR-4442, hsa-miR-1915-3p, hsa-miR-4687- at least one or more selected from the group consisting of miR-92b-3p and hsa-miR-92b-3p miRNA can also be preferably used as a target nucleic acid.

[0277] The miRNAs include, for example, those of SEQ ID NOs: 1 to 122, 349 to 383, and 464 to 4 A human gene containing a base sequence represented by any one of 73 and 492 to 494 (i.e., hsa-miR-6893-5p, hsa-miR-6075, and hsa-mi R-6820-5p, hsa-miR-4294, hsa-miR-6729-5p, h sa-miR-4476, hsa-miR-6836-3p, hsa-miR-6765 -3p, hsa-miR-6799-5p, hsa-miR-4530, hsa-miR -7641, hsa-miR-4454, hsa-miR-615-5p, hsa-mi R-8073, hsa-miR-663a, hsa-miR-4634, hsa-miR -4450、hsa-miR-4792、hsa-miR-665、hsa-miR-7 975、hsa-miR-7109-5p、hsa-miR-6789-5p、hsa- miR-4497, hsa-miR-6877-5p, hsa-miR-6880-5p hsa-miR-7977, hsa-miR-4734, hsa-miR-6821 5p、hsa-miR-8089、hsa-miR-5585-3p、hsa-miR- 6085、hsa-miR-6845-5p、hsa-miR-4651、hsa-mi R-4433-3p、hsa-miR-1231、hsa-miR-4665-5p、h sa-miR-7114-5p、hsa-miR-1238-5p、hsa-miR-8 069、hsa-miR-4732-5p、hsa-miR-619-5p、hsa-m iR-3622a-5p、hsa-miR-1260a、hsa-miR-6741-5 p、hsa-miR-6781-5p、hsa-miR-6125、hsa-miR-6 805-5p、hsa-miR-6132、hsa-miR-6872-3p、hsa- miR-6875-5p、hsa-miR-1908-3p、hsa-miR-4433 b-3p, hsa-miR-4736, hsa-miR-5100, hsa-miR-6 724-5p、hsa-miR-7107-5p、hsa-miR-6726-5p、h sa-miR-3185, hsa-miR-4638-5p, hsa-miR-1273 g-3p、hsa-miR-6778-5p、hsa-miR-328-5p、hsa- miR-3679-3p、hsa-miR-1228-3p、hsa-miR-6779 -5p、hsa-miR-4723-5p、hsa-miR-6850-5p、hsa- miR-760、hsa-miR-7704、hsa-miR-8072、hsa-mi R-4486、hsa-miR-1913、hsa-miR-4656、hsa-miR -1260b、hsa-miR-7106-5p、hsa-miR-6889-5p、h sa-miR-6780b-5p、hsa-miR-6090、hsa-miR-453 4, hsa-miR-4449, hsa-miR-5195-3p, hsa-miR-1 202、hsa-miR-4467、hsa-miR-6515-3p、hsa-miR -4281、hsa-miR-4505、hsa-miR-4484、hsa-miR- 6805-3p、hsa-miR-3135b、hsa-miR-3162-5p、hs a-miR-6768-5p、hsa-miR-6721-5p、hsa-miR-12 27-5p、hsa-miR-6722-3p、hsa-miR-4286、hsa-m iR-4746-3p、hsa-miR-6727-5p、hsa-miR-6816- 5p、hsa-miR-4741、hsa-miR-4508、hsa-miR-940 hsa-miR-4327, hsa-miR-4665-3p, hsa-miR-71 8、hsa-miR-125a-3p、hsa-miR-204-3p、hsa-miR -1469、hsa-miR-575、hsa-miR-150-3p、hsa-miR -423-5p、hsa-miR-564、hsa-miR-3188、hsa-miR -1246、hsa-miR-602、hsa-miR-1290、hsa-miR-1 6-5p、hsa-miR-451a、hsa-miR-24-3p、hsa-miR- 187-5p, hsa-miR-1908-5p, hsa-miR-371a-5p, h sa-miR-550a-5p, hsa-miR-4417, hsa-miR-4707 -5p, hsa-miR-7847-3p, hsa-miR-2861, hsa-miR -4513, hsa-miR-7111-5p, hsa-miR-6777-5p, hs a-miR-7113-3p, hsa-miR-4648, hsa-miR-3184- 5p, hsa-miR-4271, hsa-miR-6791-5p, hsa-miR- 642a-3p, hsa-miR-7108-5p, hsa-miR-128-1-5p 、hsa-miR-5196-5p, hsa-miR-3178, hsa-miR-36 56, hsa-miR-92a-2-5p, hsa-miR-6769b-5p, hsa -miR-4689, hsa-miR-6076, hsa-miR-92b-5p, hs a-miR-6774-5p, hsa-miR-486-3p, hsa-miR-680 6-5p, hsa-miR-6842-5p, hsa-miR-6716-5p, hsa -miR-557, hsa-miR-4673, hsa-miR-4674, hsa-m iR-4442, hsa-miR-1915-3p, hsa-miR-4687-3p, hsa-miR-92b-3p, hsa-miR-1203, hsa-miR-663b 、hsa-miR-4258, hsa-miR-4649-5p, hsa-miR-45 16, hsa-miR-3619-3p, hsa-miR-6826-5p, hsa-m iR-6757-5p, hsa-miR-3131, hsa-miR-1343-3p, hsa-miR-6775-5p, hsa-miR-6813-5p and hsa-miR -3940-5p), its homologues, its transcription products, and / or its variants or derivatives Here, genes, homologs, transcripts, variants and derivatives are as defined above. is.

[0278] A preferred target nucleic acid is a human gene comprising a base sequence represented by any one of SEQ ID NOs: 1 to 499. A gene, its transcription product, more preferably the transcription product, i.e., miRNA, its precursor R It is a pri-miRNA or pre-miRNA that is a NA.

[0279] The first target gene is the hsa-miR-6893-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0280] The second target gene is the hsa-miR-6075 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be a marker for pancreatic cancer.

[0281] The third target gene is the hsa-miR-6820-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0282] The fourth target gene is the hsa-miR-4294 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be a marker for pancreatic cancer.

[0283] The fifth target gene is the hsa-miR-6729-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0284] The sixth target gene is the hsa-miR-4476 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be a marker for pancreatic cancer.

[0285] The seventh target gene is the hsa-miR-6836-3p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0286] The eighth target gene is the hsa-miR-6765-3p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0287] The ninth target gene is the hsa-miR-6799-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0288] The tenth target gene is the hsa-miR-4530 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0289] The 11th target gene is the hsa-miR-7641 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0290] The 12th target gene is the hsa-miR-4454 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0291] The 13th target gene is the hsa-miR-615-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0292] The 14th target gene is the hsa-miR-8073 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0293] The 15th target gene is the hsa-miR-663a gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0294] The 16th target gene is the hsa-miR-4634 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0295] The 17th target gene is the hsa-miR-4450 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0296] The 18th target gene is the hsa-miR-4792 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0297] The 19th target gene is the hsa-miR-665 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be a marker for pancreatic cancer.

[0298] The 20th target gene is the hsa-miR-7975 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0299] The 21st target gene is the hsa-miR-7109-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0300] The 22nd target gene is the hsa-miR-6789-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0301] The 23rd target gene is the hsa-miR-4497 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0302] The 24th target gene is the hsa-miR-6877-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0303] The 25th target gene is the hsa-miR-6880-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0304] The 26th target gene is the hsa-miR-7977 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0305] The 27th target gene is the hsa-miR-4734 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0306] The 28th target gene is the hsa-miR-6821-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0307] The 29th target gene is the hsa-miR-8089 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0308] The 30th target gene is the hsa-miR-5585-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0309] The 31st target gene is the hsa-miR-6085 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0310] The 32nd target gene is the hsa-miR-6845-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0311] The 33rd target gene is the hsa-miR-4651 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0312] The 34th target gene is the hsa-miR-4433-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0313] The 35th target gene is the hsa-miR-1231 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0314] The 36th target gene is the hsa-miR-4665-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0315] The 37th target gene is the hsa-miR-7114-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0316] The 38th target gene is the hsa-miR-1238-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0317] The 39th target gene is the hsa-miR-8069 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0318] The 40th target gene is the hsa-miR-4732-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0319] The 41st target gene is the hsa-miR-619-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0320] The 42nd target gene is the hsa-miR-3622a-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0321] The 43rd target gene is the hsa-miR-1260a gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0322] The 44th target gene is the hsa-miR-6741-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0323] The 45th target gene is the hsa-miR-6781-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0324] The 46th target gene is the hsa-miR-6125 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0325] The 47th target gene is the hsa-miR-6805-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0326] The 48th target gene is the hsa-miR-6132 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0327] The 49th target gene is the hsa-miR-6872-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0328] The 50th target gene is the hsa-miR-6875-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0329] The 51st target gene is the hsa-miR-1908-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0330] The 52nd target gene is the hsa-miR-4433b-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0331] The 53rd target gene is the hsa-miR-4736 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0332] The 54th target gene is the hsa-miR-5100 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0333] The 55th target gene is the hsa-miR-6724-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0334] The 56th target gene is the hsa-miR-7107-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0335] The 57th target gene is the hsa-miR-6726-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0336] The 58th target gene is the hsa-miR-3185 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0337] The 59th target gene is the hsa-miR-4638-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0338] The 60th target gene is the hsa-miR-1273g-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0339] The 61st target gene is the hsa-miR-6778-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0340] The 62nd target gene is the hsa-miR-328-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. There are no known reports that altered expression of transcripts can be a marker for pancreatic cancer.

[0341] The 63rd target gene is the hsa-miR-3679-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0342] The 64th target gene is the hsa-miR-1228-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0343] The 65th target gene is the hsa-miR-6779-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0344] The 66th target gene is the hsa-miR-4723-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0345] The 67th target gene is the hsa-miR-6850-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0346] The 68th target gene is the hsa-miR-760 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be a marker for pancreatic cancer.

[0347] The 69th target gene is the hsa-miR-7704 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0348] The 70th target gene is the hsa-miR-8072 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0349] The 71st target gene is the hsa-miR-4486 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0350] The 72nd target gene is the hsa-miR-1913 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0351] The 73rd target gene is the hsa-miR-4656 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0352] The 74th target gene is the hsa-miR-1260b gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0353] The 75th target gene is the hsa-miR-7106-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0354] The 76th target gene is the hsa-miR-6889-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0355] The 77th target gene is the hsa-miR-6780b-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0356] The 78th target gene is the hsa-miR-6090 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0357] The 79th target gene is the hsa-miR-4534 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0358] The 80th target gene is the hsa-miR-4449 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0359] The 81st target gene is the hsa-miR-5195-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0360] The 82nd target gene is the hsa-miR-1202 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0361] The 83rd target gene is the hsa-miR-4467 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0362] The 84th target gene is the hsa-miR-6515-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0363] The 85th target gene is the hsa-miR-4281 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0364] The 86th target gene is the hsa-miR-4505 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0365] The 87th target gene is the hsa-miR-4484 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0366] The 88th target gene is the hsa-miR-6805-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0367] The 89th target gene is the hsa-miR-3135b gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0368] The 90th target gene is the hsa-miR-3162-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0369] The 91st target gene is the hsa-miR-6768-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0370] The 92nd target gene is the hsa-miR-6721-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0371] The 93rd target gene is the hsa-miR-1227-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0372] The 94th target gene is the hsa-miR-6722-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0373] The 95th target gene is the hsa-miR-4286 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0374] The 96th target gene is the hsa-miR-4746-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0375] The 97th target gene is the hsa-miR-6727-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0376] The 98th target gene is the hsa-miR-6816-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0377] The 99th target gene is the hsa-miR-4741 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0378] The 100th target gene is the hsa-miR-4508 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0379] The 101st target gene is the hsa-miR-940 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0380] The 102nd target gene is the hsa-miR-4327 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0381] The 103rd target gene is the hsa-miR-4665-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0382] The 104th target gene is the hsa-miR-718 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0383] The 105th target gene is the hsa-miR-125a-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcripts of the gene may be a marker for pancreatic cancer (see above). The above-mentioned Patent Document 1).

[0384] The 106th target gene is the hsa-miR-204-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. It has been reported that changes in the expression of transcripts can be markers for pancreatic cancer (see above). Patent document 2).

[0385] The 107th target gene is the hsa-miR-1469 gene, its homologs, and their or their variants or derivatives. It has been reported that changes in the expression of these products can be markers for pancreatic cancer (see above). Patent document 4).

[0386] The 108th target gene is the hsa-miR-575 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. It has been reported that changes in the expression of these substances can be markers for pancreatic cancer (see the above patent). Reference 3).

[0387] The 109th target gene is the hsa-miR-150-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. It has been reported that changes in the expression of transcripts can be markers for pancreatic cancer (see above). Non-patent document 4).

[0388] The 110th target gene is the hsa-miR-423-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. It has been reported that changes in the expression of transcripts can be markers for pancreatic cancer (see above). Patent document 2).

[0389] The 111th target gene is the hsa-miR-564 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. It has been reported that changes in the expression of proteins can be markers for pancreatic cancer (see above for non-specific Permitted document 4).

[0390] The 112th target gene is the hsa-miR-3188 gene, its homologs, and their or their variants or derivatives. It has been reported that changes in the expression of these products can be markers for pancreatic cancer (see above). Patent document 5).

[0391] The 113th target gene is the hsa-miR-1246 gene, its homologs, and their or their variants or derivatives. It has been reported that changes in the expression of these products can be markers for pancreatic cancer (see above). Patent document 4).

[0392] The 114th target gene is the hsa-miR-602 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. It has been reported that changes in the expression of proteins can be markers for pancreatic cancer (see above for non-specific Reference 7).

[0393] The 115th target gene is the hsa-miR-1290 gene, its homologs, and their or their variants or derivatives. It has been reported that changes in the expression of these products can be markers for pancreatic cancer (see above). Patent document 6).

[0394] The 116th target gene is the hsa-miR-16-5p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. It has been reported that changes in the expression of transcripts can be markers for pancreatic cancer (see above). Patent document 3).

[0395] The 117th target gene is the hsa-miR-451a gene, its homologs, and their or their variants or derivatives. It has been reported that changes in the expression of these products can be markers for pancreatic cancer (see above). Permitted document 4).

[0396] The 118th target gene is the hsa-miR-24-3p gene, its homologs, and These are transcription products of the genes, or their variants or derivatives. It has been reported that altered expression of transcripts can be a marker for pancreatic cancer (see above). Patent document 3).

[0397] The 119th target gene is the hsa-miR-187-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. It has been reported that changes in the expression of transcripts can be markers for pancreatic cancer (see above). Patent document 5).

[0398] The 120th target gene is the hsa-miR-1908-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcripts of the gene may be a marker for pancreatic cancer (see above). The following non-patent document 4).

[0399] The 121st target gene is the hsa-miR-371a-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcripts of the gene may be a marker for pancreatic cancer (see above). The following non-patent document 4).

[0400] The 122nd target gene is the hsa-miR-550a-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcripts of the gene may be a marker for pancreatic cancer (see above). See the above non-patent document 6).

[0401] The 123rd target gene is the hsa-miR-4417 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0402] The 124th target gene is the hsa-miR-4707-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0403] The 125th target gene is the hsa-miR-7847-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0404] The 126th target gene is the hsa-miR-2861 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0405] The 127th target gene is the hsa-miR-4513 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0406] The 128th target gene is the hsa-miR-7111-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0407] The 129th target gene is the hsa-miR-6777-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0408] The 130th target gene is the hsa-miR-7113-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0409] The 131st target gene is the hsa-miR-4648 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0410] The 132nd target gene is the hsa-miR-3184-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0411] The 133rd target gene is the hsa-miR-4271 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0412] The 134th target gene is the hsa-miR-6791-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0413] The 135th target gene is the hsa-miR-642a-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0414] The 136th target gene is the hsa-miR-7108-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0415] The 137th target gene is the hsa-miR-128-1-5p gene and its homologs , their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer. .

[0416] The 138th target gene is the hsa-miR-5196-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0417] The 139th target gene is the hsa-miR-3178 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0418] The 140th target gene is the hsa-miR-3656 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0419] The 141st target gene is the hsa-miR-92a-2-5p gene and its homologs , their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer. .

[0420] The 142nd target gene is the hsa-miR-6769b-5p gene and its homologs , their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer. .

[0421] The 143rd target gene is the hsa-miR-4689 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0422] The 144th target gene is the hsa-miR-6076 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0423] The 145th target gene is the hsa-miR-92b-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0424] The 146th target gene is the hsa-miR-6774-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0425] The 147th target gene is the hsa-miR-486-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0426] The 148th target gene is the hsa-miR-6806-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0427] The 149th target gene is the hsa-miR-6842-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0428] The 150th target gene is the hsa-miR-6716-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0429] The 151st target gene is the hsa-miR-557 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these proteins could be markers for pancreatic cancer.

[0430] The 152nd target gene is the hsa-miR-4673 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0431] The 153rd target gene is the hsa-miR-4674 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0432] The 154th target gene is the hsa-miR-4442 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0433] The 155th target gene is the hsa-miR-1915-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0434] The 156th target gene is the hsa-miR-4687-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0435] The 157th target gene is the hsa-miR-92b-3p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for pancreatic cancer.

[0436] The 158th target gene is the hsa-miR-1203 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0437] The 159th target gene is the hsa-mir-663b gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0438] The 160th target gene is the hsa-mir-4258 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0439] The 161st target gene is the hsa-mir-4649 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0440] The 162nd target gene is the hsa-mir-4516 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0441] The 163rd target gene is the hsa-mir-3619 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0442] The 164th target gene is the hsa-mir-6826 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0443] The 165th target gene is the hsa-mir-6757 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0444] The 166th target gene is the hsa-mir-3131 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0445] The 167th target gene is the hsa-mir-1343 gene, its homologs, and their or their variants or derivatives. There are no known reports that altered expression of these products could be a marker for pancreatic cancer.

[0446] The 168th target gene is the hsa-miR-6775-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0447] The 169th target gene is the hsa-miR-6813-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0448] The 170th target gene is the hsa-miR-3940-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for pancreatic cancer.

[0449] 2. Nucleic acid probes or primers for detecting pancreatic cancer In the present invention, a nucleic acid capable of specifically binding to a target nucleic acid as the pancreatic cancer marker is The acid can be used as a nucleic acid, such as a nucleic acid probe or primer, for detecting or diagnosing pancreatic cancer. It can be used as such.

[0450] In the present invention, the use of a method for detecting or diagnosing pancreatic cancer Possible nucleic acid probes or primers include human-derived hs as target nucleic acids for pancreatic cancer. a-miR-6893-5p, hsa-miR-6075, hsa-miR-6820- 5p, hsa-miR-4294, hsa-miR-6729-5p, hsa-miR- 4476, hsa-miR-6836-3p, hsa-miR-6765-3p, hsa -miR-6799-5p, hsa-miR-4530, hsa-miR-7641, h sa-miR-4454, hsa-miR-615-5p, hsa-miR-8073, hsa-miR-663a, hsa-miR-4634, hsa-miR-4450, h sa-miR-4792, hsa-miR-665, hsa-miR-7975, hsa -miR-7109-5p, hsa-miR-6789-5p, hsa-miR-449 7, hsa-miR-6877-5p, hsa-miR-6880-5p, hsa-mi R-7977, hsa-miR-4734, hsa-miR-6821-5p, hsa- miR-8089, hsa-miR-5585-3p, hsa-miR-6085, hs a-miR-6845-5p、hsa-miR-4651、hsa-miR-4433- 3p、hsa-miR-1231、hsa-miR-4665-5p、hsa-miR- 7114-5p、hsa-miR-1238-5p、hsa-miR-8069、hsa -miR-4732-5p、hsa-miR-619-5p、hsa-miR-3622 a-5p、hsa-miR-1260a、hsa-miR-6741-5p、hsa-m iR-6781-5p、hsa-miR-6125、hsa-miR-6805-5p、 hsa-miR-6132、hsa-miR-6872-3p、hsa-miR-687 5-5p、hsa-miR-1908-3p、hsa-miR-4433b-3p、hs a-miR-4736、hsa-miR-5100、hsa-miR-6724-5p、 hsa-miR-7107-5p、hsa-miR-6726-5p、hsa-miR- 3185、hsa-miR-4638-5p、hsa-miR-1273g-3p、hs a-miR-6778-5p、hsa-miR-328-5p、hsa-miR-367 9-3p、hsa-miR-1228-3p、hsa-miR-6779-5p、hsa -miR-4723-5p、hsa-miR-6850-5p、hsa-miR-760 hsa-miR-7704, hsa-miR-8072, hsa-miR-4486 hsa-miR-1913、hsa-miR-4656、hsa-miR-1260b、 hsa-miR-7106-5p、hsa-miR-6889-5p、hsa-miR- 6780b-5p, hsa-miR-6090, hsa-miR-4534, hsa-m iR-4449, hsa-miR-5195-3p, hsa-miR-1202, hsa -miR-4467, hsa-miR-6515-3p, hsa-miR-4281, h sa-miR-4505, hsa-miR-4484, hsa-miR-6805-3p , hsa-miR-3135b, hsa-miR-3162-5p, hsa-miR-6 768-5p, hsa-miR-6721-5p, hsa-miR-1227-5p, h sa-miR-6722-3p, hsa-miR-4286, hsa-miR-4746 -3p, hsa-miR-6727-5p, hsa-miR-6816-5p, hsa- miR-4741, hsa-miR-4508, hsa-miR-940, hsa-mi R-4327, hsa-miR-4665-3p, hsa-miR-718, hsa-m iR-1203, hsa-miR-663b, hsa-miR-4258, hsa-mi R-4649-5p, hsa-miR-4516, hsa-miR-3619-3p, h sa-miR-6826-5p, hsa-miR-6757-5p, hsa-miR-3 131, hsa-miR-1343-3p, hsa-miR-6775-5p, hsa- miR-6813-5p and hsa-miR-3940-5p, or a combination thereof hsa-miR-125, which may optionally be combined with a-3p, hsa-miR-204-3p, hsa-miR-1469, hsa-miR -575, hsa-miR-150-3p, hsa-miR-423-5p, hsa-m iR-564, hsa-miR-3188, hsa-miR-1246, hsa-miR -602, hsa-miR-1290, hsa-miR-16-5p, hsa-miR- 451a, hsa-miR-24-3p, hsa-miR-187-5p, hsa-mi R-1908-5p, hsa-miR-371a-5p, and hsa-miR-550 a-5p, or a combination thereof, and possibly in combination with them hsa-miR-4417, hsa-miR-4707-5p, hsa-mi R-7847-3p, hsa-miR-2861, hsa-miR-4513, hsa- miR-7111-5p, hsa-miR-6777-5p, hsa-miR-7113 -3p, hsa-miR-4648, hsa-miR-3184-5p, hsa-miR -4271, hsa-miR-6791-5p, hsa-miR-642a-3p, hs a-miR-7108-5p, hsa-miR-128-1-5p, hsa-miR-5 196-5p, hsa-miR-3178, hsa-miR-3656, hsa-miR -92a-2-5p, hsa-miR-6769b-5p, hsa-miR-4689, hsa-miR-6076, hsa-miR-92b-5p, hsa-miR-6774 -5p, hsa-miR-486-3p, hsa-miR-6806-5p, hsa-m iR-6842-5p, hsa-miR-6716-5p, hsa-miR-557, h sa-miR-4673, hsa-miR-4674, hsa-miR-4442, hs a-miR-1915-3p, hsa-miR-4687-3p and hsa-miR-9 2b-3p, or any combination thereof, their homologs, their transcripts, or The presence, expression level or abundance of these mutants or derivatives is qualitatively and / or quantitatively measured. This makes it possible to do so.

[0451] The target nucleic acid is a nucleic acid having a higher affinity for the target nucleic acid in a subject suffering from pancreatic cancer compared to a healthy subject. Depending on the species, the expression levels may increase or decrease (hereinafter, Therefore, the composition of the present invention can be used to treat pancreatic cancer in patients suspected of having pancreatic cancer. The expression level of the target nucleic acid is measured in body fluids derived from a subject (e.g., a human) and body fluids derived from a healthy subject. These can be used effectively to detect pancreatic cancer by comparing the results. The composition of the present invention is a mixture of a body fluid from a subject (e.g., a human) suspected of having pancreatic cancer and a pancreatic cancer cell line. Body fluids from patients with intestinal cancer, stomach cancer, esophageal cancer, liver cancer, and benign pancreatic and biliary diseases The expression levels of the target nucleic acids are measured for each of the above-mentioned cancers and benign diseases, and the results are compared. Therefore, it can be effectively used to specifically detect pancreatic cancer.

[0452] Nucleic acid probes or primers that can be used in the present invention are those represented by SEQ ID NOs: 1 to 104, 464 to 4 A polynucleotide consisting of at least one of the base sequences represented by 73, and 492 to 494. Nucleic acid probes capable of specifically binding to the nucleotides of SEQ ID NOs: 1 to 104, 464 to 473 and a polynucleotide consisting of at least one of the base sequences 492 to 494. Primers for amplification.

[0453] Nucleic acid probes or primers that can be used in the present invention further include those of SEQ ID NOs: 105 to 122. A nucleic acid capable of specifically binding to a polynucleotide consisting of at least one of the base sequences represented by A probe or a base sequence represented by at least one of SEQ ID NOs: 105 to 122 The sequence may include primers for amplifying a polynucleotide comprising the sequence.

[0454] Nucleic acid probes or primers that can be used in the present invention further include those of SEQ ID NOs: 349 to 383. A nucleic acid capable of specifically binding to a polynucleotide consisting of at least one of the base sequences represented by A probe or a base sequence represented by at least one of SEQ ID NOs: 349 to 383 The nucleic acid sequence may further comprise primers for amplifying a polynucleotide comprising the sequence.

[0455] Specifically, the nucleic acid probes or primers are those represented by SEQ ID NOs: 1 to 122, 349 to 3 83, 464-473, and 492-494, or the corresponding base sequence A group of polynucleotides containing the base sequence in which u is t and its complementary polynucleotides nucleotide group, DNA consisting of a base sequence complementary to the base sequence, and stringent A group of polynucleotides that hybridize under the conditions described below and their complementary polynucleotides The base sequences of the nucleotide groups and the polynucleotide groups are preferably 15 or more. One or more polynucleotides selected from a group of polynucleotides containing 17 or more consecutive bases. These polynucleotides comprise a combination of nucleotides. It can be used as a nucleic acid probe and primer for detecting cancer markers.

[0456] More specifically, examples of nucleic acid probes or primers that can be used in the present invention include the following: One or more polynucleotides selected from the group consisting of any of the polynucleotides (a) to (e). It is a nucleotide. (a) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A polynucleotide consisting of a base sequence, or a base sequence in which u is t a nucleotide sequence of 15 or more consecutive bases, a variant thereof, a derivative thereof, or a fragment thereof, (b) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 a polynucleotide comprising a base sequence; (c) Represented by any of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A base sequence complementary to the base sequence, or the base sequence in which u is replaced by t a polynucleotide comprising 15 or more consecutive bases, a variant thereof, a derivative thereof, or The fragment, (d) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A base sequence complementary to the base sequence, or the base sequence in which u is t, a polynucleotide comprising: (e) A polynucleotide that binds to any one of the polynucleotides (a) to (d) under stringent conditions. Hybridizing polynucleotide.

[0457] The nucleic acid probe or primer that can be used in the present invention further includes the above-mentioned polynucleotide ( In addition to at least one polynucleotide selected from any of a) to (e), It may contain any of the polynucleotides (f) to (j) below. (f) a base sequence represented by any one of SEQ ID NOs: 105 to 122 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122; (h) a base sequence represented by any one of SEQ ID NOs: 105 to 122, or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, and a variant thereof a fragment thereof containing 15 or more consecutive bases, (i) a base sequence represented by any one of SEQ ID NOs: 105 to 122, or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; and (j) A method for detecting a polynucleotide that is hybridized with any one of the polynucleotides (f) to (i) under stringent conditions. Hybridizing polynucleotide.

[0458] The nucleic acid probe or primer that can be used in the present invention further includes the above-mentioned polynucleotide ( In addition to at least one polynucleotide selected from any of a) to (j), It may contain any of the polynucleotides (k) to (o) below. (k) a base sequence represented by any one of SEQ ID NOs: 349 to 383 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 349 to 383; (m) a base sequence represented by any one of SEQ ID NOs: 349 to 383, or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, and a variant thereof a fragment thereof containing 15 or more consecutive bases, (n) a base sequence represented by any one of SEQ ID NOs: 349 to 383, or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; and (o) a polynucleotide that binds to any one of the polynucleotides (k) to (n) under stringent conditions; Hybridizing polynucleotide.

[0459] In the above polynucleotide, "a fragment containing 15 or more consecutive bases" means each polynucleotide. In a base sequence of a polynucleotide, for example, 15 consecutive bases or less than the total number of bases in the sequence, It may contain a range of base numbers, such as 7 to less than the total number of bases in the sequence, or 19 to less than the total number of bases in the sequence. The present invention can be implemented in the following ways, but is not limited to these.

[0460] The polynucleotides or fragments thereof used in the present invention may be DNA. RNA may also be used.

[0461] The above polynucleotides that can be used in the present invention can be synthesized by DNA recombination techniques, PCR methods, DNA / It can be prepared using common techniques such as methods using an automatic RNA synthesizer.

[0462] The DNA recombination technique and the PCR method are described, for example, in Ausubel et al., Current Proc. otocols in Molecular Biology, John Wille y & Sons, US (1993); Sambrook et al., Molecula r Cloning A Laboratory Manual, Cold Spr. Harbor Laboratory Press, US (1989), etc. The techniques described in can be used.

[0463] Represented by SEQ ID NOs: 1 to 122, 349 to 383, 464 to 473, and 492 to 494 hsa-miR-6893-5p, hsa-miR-6075, and hsa -miR-6820-5p, hsa-miR-4294, hsa-miR-6729-5 p、hsa-miR-4476、hsa-miR-6836-3p、hsa-miR-6 765-3p、hsa-miR-6799-5p、hsa-miR-4530、hsa- miR-7641, hsa-miR-4454, hsa-miR-615-5p, hsa -miR-8073、hsa-miR-663a、hsa-miR-4634、hsa- miR-4450, hsa-miR-4792, hsa-miR-665, hsa-mi R-7975、hsa-miR-7109-5p、hsa-miR-6789-5p、h sa-miR-4497、hsa-miR-6877-5p、hsa-miR-6880 -5p、hsa-miR-7977、hsa-miR-4734、hsa-miR-68 21-5p、hsa-miR-8089、hsa-miR-5585-3p、hsa-m iR-6085、hsa-miR-6845-5p、hsa-miR-4651、hsa -miR-4433-3p、hsa-miR-1231、hsa-miR-4665-5 p、hsa-miR-7114-5p、hsa-miR-1238-5p、hsa-mi R-8069、hsa-miR-4732-5p、hsa-miR-619-5p、hs a-miR-3622a-5p、hsa-miR-1260a、hsa-miR-674 1-5p、hsa-miR-6781-5p、hsa-miR-6125、hsa-mi R-6805-5p、hsa-miR-6132、hsa-miR-6872-3p、h sa-miR-6875-5p、hsa-miR-1908-3p、hsa-miR-4 433b-3p、hsa-miR-4736、hsa-miR-5100、hsa-mi R-6724-5p、hsa-miR-7107-5p、hsa-miR-6726-5 p、hsa-miR-3185、hsa-miR-4638-5p、hsa-miR-1 273g-3p、hsa-miR-6778-5p、hsa-miR-328-5p、h sa-miR-3679-3p、hsa-miR-1228-3p、hsa-miR-6 779-5p、hsa-miR-4723-5p、hsa-miR-6850-5p、h sa-miR-760、hsa-miR-7704、hsa-miR-8072、hsa -miR-4486、hsa-miR-1913、hsa-miR-4656、hsa- miR-1260b、hsa-miR-7106-5p、hsa-miR-6889-5 p、hsa-miR-6780b-5p、hsa-miR-6090、hsa-miR- 4534、hsa-miR-4449、hsa-miR-5195-3p、hsa-mi R-1202、hsa-miR-4467、hsa-miR-6515-3p、hsa- miR-4281, hsa-miR-4505, hsa-miR-4484, hsa-m iR-6805-3p、hsa-miR-3135b、hsa-miR-3162-5p hsa-miR-6768-5p, hsa-miR-6721-5p, hsa-miR -1227-5p、hsa-miR-6722-3p、hsa-miR-4286、hs a-miR-4746-3p、hsa-miR-6727-5p、hsa-miR-68 16-5p、hsa-miR-4741、hsa-miR-4508、hsa-miR- 940、hsa-miR-4327、hsa-miR-4665-3p、hsa-miR -718、hsa-miR-125a-3p、hsa-miR-204-3p、hsa- miR-1469、hsa-miR-575、hsa-miR-150-3p、hsa- miR-423-5p、hsa-miR-564、hsa-miR-3188、hsa- miR-1246, hsa-miR-602, hsa-miR-1290, hsa-mi R-16-5p、hsa-miR-451a、hsa-miR-24-3p、hsa-m iR-187-5p、hsa-miR-1908-5p、hsa-miR-371a-5 p、hsa-miR-550a-5p、hsa-miR-4417、hsa-miR-4 707-5p、hsa-miR-7847-3p、hsa-miR-2861、hsa- miR-4513, hsa-miR-7111-5p, hsa-miR-6777-5p hsa-miR-7113-3p, hsa-miR-4648, hsa-miR-31 84-5p、hsa-miR-4271、hsa-miR-6791-5p、hsa-m iR-642a-3p、hsa-miR-7108-5p、hsa-miR-128-1 -5p、hsa-miR-5196-5p、hsa-miR-3178、hsa-miR -3656、hsa-miR-92a-2-5p、hsa-miR-6769b-5p、 hsa-miR-4689, hsa-miR-6076, hsa-miR-92b-5p 、hsa-miR-6774-5p、hsa-miR-486-3p、hsa-miR- 6806-5p、hsa-miR-6842-5p、hsa-miR-6716-5p、 hsa-miR-557, hsa-miR-4673, hsa-miR-4674, hs a-miR-4442、hsa-miR-1915-3p、hsa-miR-4687- 3p、hsa-miR-92b-3p、hsa-miR-1203、hsa-miR-6 63b, hsa-miR-4258, hsa-miR-4649-5p, hsa-miR -4516, hsa-miR-3619-3p, hsa-miR-6826-5p, hs a-miR-6757-5p, hsa-miR-3131, hsa-miR-1343- 3p, hsa-miR-6775-5p, hsa-miR-6813-5p and hsa- miR-3940-5p is known, and as mentioned above, its acquisition method is also known. Therefore, by cloning this gene, it is possible to obtain a nucleic acid probe or can generate polynucleotides as primers.

[0464] Such nucleic acid probes or primers can be chemically synthesized using an automated DNA synthesizer. This synthesis is generally carried out using the phosphoramidite method, which The automated DNA synthesizer can automatically synthesize single-stranded DNA up to about 100 bases. For example, Polygen, ABI, Applied BioSystems, etc. It is commercially available.

[0465] Alternatively, the polynucleotides of the present invention can be produced by cDNA cloning techniques. cDNA cloning technology is also possible, for example, microRNA cloning You can use Kit Wako etc.

[0466] Here, SEQ ID NOs: 1 to 122, 349 to 383, 464 to 473, and 492 to 494 A nucleic acid probe for detecting a polynucleotide having a base sequence represented by any one of The sequence of the primer does not exist in vivo as miRNA or its precursor. For example, the base sequences represented by SEQ ID NO: 36 and SEQ ID NO: 103 are identical to those represented by SEQ ID NO: 159. It is produced from a precursor that has a hairpin-like structure as shown in Figure 1. The base sequences represented by SEQ ID NO: 36 and SEQ ID NO: 103 have mismatched sequences with each other. Therefore, the complete sequence of the base sequence represented by SEQ ID NO: 36 or SEQ ID NO: 103 is A base sequence complementary to SEQ ID NO: 1 to 1 is not naturally produced in vivo. A base represented by any one of 22, 349 to 383, 464 to 473, and 492 to 494 The nucleic acid probes and primers used to detect the sequences are artificial base sequences that do not exist in vivo. It will have columns.

[0467] 3. Pancreatic cancer detection kit or device The present invention also relates to a method for measuring a target nucleic acid that is a pancreatic cancer marker, comprising the steps of: Polynucleotides that can be used as nucleic acid probes or primers (including mutants, fragments, or a derivative thereof. to provide.

[0468] The target nucleic acid that is a pancreatic cancer marker in the present invention is at least one selected from the following Group A: Both are nucleic acids.

[0469] Group A: miR-6893-5p, miR-6075, miR-6820-5p, miR-42 94, miR-6729-5p, miR-4476, miR-6836-3p, miR- 6765-3p, miR-6799-5p, miR-4530, miR-7641, mi R-4454, miR-615-5p, miR-8073, miR-663a, miR- 4634、miR-4450、miR-4792、miR-665、miR-7975、 miR-7109-5p, miR-6789-5p, miR-4497, miR-687 7-5p、miR-6880-5p、miR-7977、miR-4734、miR-6 821-5p、miR-8089、miR-5585-3p、miR-6085、miR -6845-5p、miR-4651、miR-4433-3p、miR-1231、m iR-4665-5p、miR-7114-5p、miR-1238-5p、miR-8 069、miR-4732-5p、miR-619-5p、miR-3622a-5p、 miR-1260a, miR-6741-5p, miR-6781-5p, miR-61 25、miR-6805-5p、miR-6132、miR-6872-3p、miR- 6875-5p、miR-1908-3p、miR-4433b-3p、miR-473 6, miR-5100, miR-6724-5p, miR-7107-5p, miR-6 726-5p、miR-3185、miR-4638-5p、miR-1273g-3p 、miR-6778-5p、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-4486、m iR-1913、miR-4656、miR-1260b、miR-7106-5p、m iR-6889-5p、miR-6780b-5p、miR-6090、miR-453 4, miR-4449, 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-67 68-5p, miR-6721-5p, miR-1227-5p, miR-6722-3 p, miR-4286, miR-4746-3p, miR-6727-5p, miR-6 816-5p, miR-4741, miR-4508, miR-940, miR-432 7, miR-4665-3p, miR-718, miR-1203, miR-663b, miR-4258, miR-4649-5p, miR-4516, miR-3619-3 p, miR-6826-5p, miR-6757-5p, miR-3131, miR-1 343-3p, miR-6775-5p, miR-6813-5p and miR-3940 -5p.

[0470] Additional target nucleic acids that may be used for measurement in some cases include at least one selected from Group B below: It is a single nucleic acid.

[0471] Group B: 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, mi R-371a-5p and miR-550a-5p.

[0472] Additional target nucleic acids that may be used for further measurement in some cases include at least one selected from Group C below. At least one nucleic acid.

[0473] Group C: miR-4417, miR-4707-5p, miR-7847-3p, miR-28 61, miR-4513, miR-7111-5p, miR-6777-5p, miR- 7113-3p, miR-4648, miR-3184-5p, miR-4271, mi R-6791-5p, miR-642a-3p, miR-7108-5p, miR-12 8-1-5p, 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-6 806-5p, miR-6842-5p, miR-6716-5p, miR-557, m iR-4673, miR-4674, miR-4442, miR-1915-3p, mi R-4687-3p and miR-92b-3p.

[0474] The kit or device of the present invention specifically binds to the target nucleic acid that is the pancreatic cancer marker. a nucleic acid capable of synthesizing the nucleic acid, preferably one or more selected from the polynucleotides described in 2 above; It comprises a plurality of polynucleotides or variants thereof.

[0475] Specifically, the kit or device of the present invention includes SEQ ID NOs: 1 to 104, 464 to 473, and a base sequence represented by any one of 492 to 494, or the base sequence in which u is A polynucleotide containing (or consisting of) a base sequence of t, and its complementary sequence Polynucleotides containing (or consisting of), those polynucleotides and strings Polynucleotides that hybridize under favorable conditions, or polynucleotide sequences thereof and at least one variant or fragment containing 15 or more consecutive bases of the sequence. Cut.

[0476] The kit or device of the present invention further comprises a compound represented by any one of SEQ ID NOs: 105 to 122. A base sequence, or a base sequence in which u is t in the base sequence (or a polynucleotide comprising (or consisting of) its complementary sequence; Polynucleotides that hybridize under stringent conditions with these polynucleotides. nucleotides or variants containing 15 or more consecutive bases of their polynucleotide sequences or fragments thereof.

[0477] The kit or device of the present invention further comprises a compound represented by any one of SEQ ID NOs: 349 to 383. A base sequence, or a base sequence in which u is t in the base sequence (or a polynucleotide comprising (or consisting of) its complementary sequence; Polynucleotides that hybridize under stringent conditions with these polynucleotides. nucleotides or variants containing 15 or more consecutive bases of their polynucleotide sequences or fragments thereof.

[0478] The fragments that can be contained in the kit or device of the present invention include, for example, the following fragments (1) to (3): The polynucleotide is one or more, preferably two or more, selected from the group consisting of: (1) Represented by any of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 In the base sequence, u is t or its complementary sequence, 15 or more consecutive A polynucleotide containing bases. (2) A base in which u is t in the base sequence represented by any one of SEQ ID NOs: 105 to 122 A polynucleotide containing 15 or more consecutive bases in a sequence or its complementary sequence. (3) A base in which u is t in the base sequence represented by any one of SEQ ID NOs: 349 to 383 A polynucleotide containing 15 or more consecutive bases in a sequence or its complementary sequence.

[0479] In a preferred embodiment, the polynucleotide is selected from the group consisting of SEQ ID NOs: 1 to 104, 464 to 47 3, and 492 to 494, or the base sequence A polynucleotide consisting of a base sequence in which u is t, a polynucleotide consisting of a complementary sequence thereof nucleotides, polynucleotides that hybridize to those polynucleotides under stringent conditions. nucleotides, or 15 or more thereof, preferably 17 or more, more preferably 19 or more thereof It is a variant containing consecutive bases.

[0480] In a preferred embodiment, the polynucleotide is any one of SEQ ID NOs: 105 to 122. A base sequence represented by either of the above, or a base sequence in which u is t in the base sequence, a polynucleotide comprising the sequence thereof, a polynucleotide comprising the sequence thereof, Polynucleotides that hybridize under stringent conditions with the nucleotides, or their A mutant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases. be.

[0481] In a preferred embodiment, the polynucleotide is any one of SEQ ID NOs: 349 to 383. A base sequence represented by either of the above, or a base sequence in which u is t in the base sequence, a polynucleotide consisting of the complementary sequence thereof; Polynucleotides that hybridize under stringent conditions with the nucleotides, or their A mutant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases. be.

[0482] In a preferred embodiment, the fragments are 15 or more, preferably 17 or more, more preferably It can be a polynucleotide containing 19 or more consecutive bases.

[0483] In the present invention, the size of a polynucleotide fragment is determined based on the base sequence of each polynucleotide. For example, from 15 to less than the total number of bases in the sequence, from 17 to less than the total number of bases in the sequence , the number of bases may range from 19 to less than the total number of bases in the sequence.

[0484] The above combinations constituting the kit or device of the present invention are specifically shown in Table 1. SEQ ID NOs: 1 to 122, 349 to 349 corresponding to the miRNA markers in Table 1 The above polynucleotides relating to the combinations of However, these are merely examples and various other possible combinations are possible. All such combinations are intended to be encompassed by the present invention.

[0485] In the present invention, the above-mentioned kit or device for distinguishing between pancreatic cancer and healthy subjects is Examples of the combination include the base sequences represented by the sequence numbers shown in Table 1. It is desirable to combine two or more of the above polynucleotides, and usually two combinations are used. By combining these, sufficient performance can be obtained.

[0486] Polynucleotides consisting of a base sequence or its complementary sequence for distinguishing between pancreatic cancer and healthy subjects Specific combinations of two of the nucleotides are SEQ ID NOs: 1 to 122, 349 to 383, 4 The above polynucleotide consisting of the base sequences represented by 64 to 473 and 492 to 494. Of the two combinations consisting of SEQ ID NOs: 1 to 104 and 349 to 349, the newly discovered Polynucleotides consisting of the base sequences represented by 383, 464-473, and 492-494 A combination containing at least one tide is preferred.

[0487] Furthermore, a gene encoding a polypeptide consisting of a base sequence or its complementary sequence for distinguishing between pancreatic cancer and healthy subjects is also available. As a combination of two nucleotides, SEQ ID NOs: 1, 2, 4, 7, 15, 24, 10 5, 107, 108 or a complementary sequence thereof and at least one polynucleotide selected from the group consisting of SEQ ID NO: The combination of the two polynucleotides is preferred.

[0488] The following are non-limiting examples of sequences of SEQ ID NOs: 1 to 122, 34, and 50 for distinguishing between pancreatic cancer and healthy subjects. The above fragments each consisting of the base sequences represented by 9 to 383, 464 to 473, and 492 to 494 Of the two combinations of nucleotides, the base sequence represented by SEQ ID NO: 1 is Examples of combinations containing polynucleotides consisting of the sequences thereof or complementary sequences thereof are shown below.

[0489] (1) SEQ ID NOs: 1 and 77 (markers: hsa-miR-6893-5p and hsa-mi R-6780b-5p) combination (2) SEQ ID NOs: 1 and 119 (markers: hsa-miR-6893-5p and hsa-m iR-187-5p) combination (3) SEQ ID NOs: 1 and 20 (markers: hsa-miR-6893-5p and hsa-mi R-7975) combination Furthermore, non-limiting examples include sequences of SEQ ID NOS: 1 to 122, 349, and 350 for distinguishing between pancreatic cancer and healthy subjects. The above-mentioned base sequences represented by nucleotides 383, 464, 473, and 492, 493, 494, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 53 Among the two combinations of polynucleotides, the base sequence represented by SEQ ID NO: 2 Examples of combinations containing polynucleotides consisting of the sequence or its complementary sequence are given below. .

[0490] (1) SEQ ID NOs: 2 and 105 (markers: hsa-miR-6075 and hsa-miR- 125a-3p) combination (2) SEQ ID NOs: 2 and 16 (markers: hsa-miR-6075 and hsa-miR-4 634) combination (3) SEQ ID NOs: 2 and 10 (markers: hsa-miR-6075 and hsa-miR-4 530) combination Furthermore, non-limiting examples include sequences of SEQ ID NOS: 1 to 122, 349, and 350 for distinguishing between pancreatic cancer and healthy subjects. The above-mentioned base sequences represented by nucleotides 383, 464, 473, and 492, 493, 494, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 53 Among the two combinations of polynucleotides, the base sequence represented by SEQ ID NO: 4 Examples of combinations containing polynucleotides consisting of the sequence or its complementary sequence are given below. .

[0491] (1) SEQ ID NOs: 4 and 105 (markers: hsa-miR-4294 and hsa-miR- 125a-3p) combination (2) SEQ ID NOs: 4 and 119 (markers: hsa-miR-4294 and hsa-miR- 187-5p) combination (3) SEQ ID NOs: 4 and 45 (markers: hsa-miR-4294 and hsa-miR-6 781-5p) combination Furthermore, non-limiting examples include sequences of SEQ ID NOS: 1 to 122, 349, and 350 for distinguishing between pancreatic cancer and healthy subjects. The above-mentioned base sequences represented by nucleotides 383, 464, 473, and 492, 493, 494, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 53 Among the two combinations of polynucleotides, the base sequence represented by SEQ ID NO: 7 Examples of combinations containing polynucleotides consisting of the sequence or its complementary sequence are given below. .

[0492] (1) SEQ ID NOs: 7 and 105 (markers: hsa-miR-6836-3p and hsa-m iR-125a-3p) combination (2) SEQ ID NOs: 7 and 34 (markers: hsa-miR-6836-3p and hsa-mi R-4433-3p) combination (3) SEQ ID NOs: 7 and 12 (markers: hsa-miR-6836-3p and hsa-mi R-4454) combination Furthermore, non-limiting examples include sequences of SEQ ID NOS: 1 to 122, 349, and 350 for distinguishing between pancreatic cancer and healthy subjects. The above-mentioned base sequences represented by nucleotides 383, 464, 473, and 492, 493, 494, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, Among the two combinations of polynucleotides, the salt represented by SEQ ID NO: 105 Examples of combinations containing a polynucleotide consisting of the base sequence or its complementary sequence are given below. do.

[0493] (1) SEQ ID NOs: 18 and 105 (markers: hsa-miR-4792 and hsa-miR -125a-3p) combination (2) SEQ ID NOs: 46 and 105 (markers: hsa-miR-6125 and hsa-miR -125a-3p) combination (3) SEQ ID NOs: 105 and 494 (markers: hsa-miR-125a-3p and hsa -miR-3940-5p) combination In addition, we have developed cancer-specific polymerases that can distinguish pancreatic cancer from not only healthy subjects but also other cancers. As a combination of nucleotides, for example, SEQ ID NOs: 2, 4, 6, 7, 9, 10, 25, 2 Represented by 8, 30, 31, 38, 48, 82, 103, 105, 108 and 464 A group of polynucleotides consisting of a base sequence corresponding to the above or its complementary sequence (hereinafter, this group is referred to as " At least one polynucleotide selected from the cancer type-specific polynucleotide group 1 A combination of multiple nucleotides with other polynucleotides of SEQ ID NO: is preferred.

[0494] Furthermore, we have developed cancer-specific polyclonal antibodies that can distinguish pancreatic cancer from not only healthy individuals but also other cancers. The combination of nucleotides is a polynucleotide selected from Cancer Type-Specific Polynucleotide Group 1. A combination of several polynucleotides is more preferred.

[0495] Furthermore, we have developed cancer-specific polyclonal antibodies that can distinguish pancreatic cancer from not only healthy individuals but also other cancers. The combination of nucleotides is a polynucleotide selected from Cancer Type-Specific Polynucleotide Group 1. Among the combinations of several polynucleotides, those included in Cancer Type-Specific Polynucleotide Group 1 The nucleotide sequences represented by SEQ ID NOs: 2, 4, 7, 10 and 25 or their complementary sequences A group consisting of polynucleotides consisting of sequences (hereinafter, this group is referred to as the "cancer type-specific polynucleotide group"). 2) The combination of the above cancer type-specific polynucleotides is more preferable. The number of pieces is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or Although it is possible to combine more than this number, it is more preferable to combine four or more. Normally, a combination of four will provide sufficient performance.

[0496] The following are non-limiting examples of sequences consisting of the base sequence represented by SEQ ID NO: 2 or its complementary sequence: Polynucleotide and three polynucleotides selected from cancer type-specific polynucleotide group 1 A polynucleotide consisting of a base sequence represented by the SEQ ID NO of the nucleotide or its complementary sequence. The following illustrates a combination of:

[0497] (1) SEQ ID NOs: 2, 9, 105, 7 (marker: hsa-miR-6075, hsa -miR-6799-5p, hsa-miR-125a-3p, hsa-miR-6 836-3p) combination (2) SEQ ID NOs: 2, 7, 108, 464 (marker: hsa-miR-6075, h sa-miR-6836-3p, hsa-miR-575, hsa-miR-120 3) Combination (3) SEQ ID NOs: 2, 31, 48, 38 (markers: hsa-miR-6075, hs a-miR-6085, hsa-miR-6132, hsa-miR-1238-5 p) combination (4) SEQ ID NOs: 2, 31, 28, 48 (marker: hsa-miR-6075, hs a-miR-6085, hsa-miR-6821-5p, hsa-miR-613 Combination of 2) (5) SEQ ID NOs: 2, 25, 105, 10 (marker: hsa-miR-6075, h sa-miR-6880-5p, hsa-miR-125a-3p, hsa-miR -4530) combination Furthermore, the present invention also includes, but is not limited to, a polynucleotide having the base sequence represented by SEQ ID NO: 4 or its complementary sequence. and three polynucleotides selected from cancer type-specific polynucleotide group 1. a polynucleotide consisting of a base sequence represented by the sequence number of the nucleotide sequence of the nucleotide sequence or a complementary sequence thereof; Examples of combinations are shown below.

[0498] (1) SEQ ID NOs: 4, 31, 7, 82 (marker: hsa-miR-4294, hsa -miR-6085, hsa-miR-6836-3p, hsa-miR-1202 ) combination (2) SEQ ID NOs: 4, 31, 28, 82 (marker: hsa-miR-4294, hs a-miR-6085, hsa-miR-6821-5p, hsa-miR-120 Combination of 2) (3) SEQ ID NOs: 4, 10, 7, 82 (marker: hsa-miR-4294, hsa -miR-4530, hsa-miR-6836-3p, hsa-miR-1202 ) combination (4) SEQ ID NOs: 4, 7, 82, 103 (marker: hsa-miR-4294, hs a-miR-6836-3p, hsa-miR-1202, hsa-miR-466 5-3p) combination (5) SEQ ID NOs: 4, 105, 10, 6 (marker: hsa-miR-4294, hs a-miR-125a-3p, hsa-miR-4530, hsa-miR-447 6) Combination Furthermore, the present invention also includes, but is not limited to, a polynucleotide having the base sequence represented by SEQ ID NO: 7 or its complementary sequence. and three polynucleotides selected from cancer type-specific polynucleotide group 1. a polynucleotide consisting of a base sequence represented by the sequence number of the nucleotide sequence of the nucleotide sequence or a complementary sequence thereof; Examples of combinations are shown below.

[0499] (1) SEQ ID NOs: 4, 7, 82, 101 (marker: hsa-miR-4294, hsa -miR-6836-3p, hsa-miR-1202, hsa-miR-940) combination (2) SEQ ID NOs: 4, 7, 38, 82 (markers: hsa-miR-4294, hsa- miR-6836-3p, hsa-miR-1238-5p, hsa-miR-1202 ) combination (3) SEQ ID NOs: 6, 7, 61, 68 (markers: hsa-miR-4476, hsa- miR-6836-3p, hsa-miR-6778-5p, hsa-miR-760) Combination of (4) SEQ ID NOs: 4, 7, 47, 82 (markers: hsa-miR-4294, hsa- miR-6836-3p, hsa-miR-6805-5p, hsa-miR-1202 ) combination (5) SEQ ID NOs: 4, 7, 82, 103 (marker: hsa-miR-4294, hsa -miR-6836-3p, hsa-miR-1202, hsa-miR-4665-3 p) combination Furthermore, it is not limited to a nucleic acid sequence consisting of the base sequence represented by SEQ ID NO: 10 or its complementary sequence. Polynucleotide and three polynucleotides selected from cancer type-specific polynucleotide group 1 A polynucleotide consisting of a base sequence represented by the SEQ ID NO of the nucleotide or its complementary sequence. Examples of combinations with are shown below.

[0500] (1) SEQ ID NOs: 10, 47, 90, 101 (marker: hsa-miR-4530, h sa-miR-6805-5p, hsa-miR-3162-5p, hsa-miR-9 40) combination (2) SEQ ID NOs: 10, 30, 103, 365 (marker: hsa-miR-4530, hsa-miR-5585-3p, hsa-miR-4665-3p, phsa-miR -3178) combination (3) SEQ ID NOs: 9, 10, 61, 68 (marker: hsa-miR-6799-5p, hsa-miR-4530, hsa-miR-6778-5p, hsa-miR-760 ) combination (4) SEQ ID NOs: 10, 48, 68, 90 (marker: hsa-miR-4530, hs a-miR-6132, hsa-miR-760, hsa-miR-3162-5p) combination (5) SEQ ID NOs: 10, 30, 68, 365 (marker: hsa-miR-4530, h sa-miR-5585-3p, hsa-miR-760, hsa-miR-3178) Combination of Furthermore, it is not limited to a nucleic acid sequence consisting of the base sequence represented by SEQ ID NO: 25 or its complementary sequence. Polynucleotide and three polynucleotides selected from cancer type-specific polynucleotide group 1 A polynucleotide consisting of a base sequence represented by the SEQ ID NO of the nucleotide or its complementary sequence. Examples of combinations with are shown below.

[0501] (1) SEQ ID NOs: 7, 25, 466, 47 (marker: hsa-miR-6836-3p , hsa-miR-6880-5p, hsa-miR-4258, hsa-miR-68 05-5p) combination (2) SEQ ID NOs: 7, 25, 48, 466 (marker: hsa-miR-6836-3p , hsa-miR-6880-5p, hsa-miR-6132, hsa-miR-42 58) combination (3) SEQ ID NOs: 7, 25, 28, 466 (marker: hsa-miR-6836-3p , hsa-miR-6880-5p, hsa-miR-6821-5p, hsa-miR -4258) combination (4) SEQ ID NOs: 7, 25, 30, 466 (marker: hsa-miR-6836-3p , hsa-miR-6880-5p, hsa-miR-5585-3p, hsa-miR -4258) combination (5) SEQ ID NOs: 7, 25, 31, 47 (marker: hsa-miR-6836-3p, hsa-miR-6880-5p, hsa-miR-6085, hsa-miR-680 5-5p) combination The kit or device of the present invention may contain the polynucleotide of the present invention described above ( This may include mutants, fragments, or derivatives. This includes known polynucleotides and polynucleotides that may be discovered in the future. can be done.

[0502] The kit of the present invention includes the above-described polynucleotide of the present invention and its variants. or fragments thereof, plus CEA, CA19-9, SPan-1, DUPAN-2, CA5 Known pancreatic cancer tests such as 0, CA242, TAG-72, urinary fucose, POA, and TPS Antibodies for measuring the markers under investigation can also be included.

[0503] The polynucleotides and variants or fragments thereof contained in the kit of the present invention can be individually Or they may be packaged in any combination in different containers.

[0504] The kit of the present invention includes a nucleic acid extractor for extracting nucleic acid (e.g., total RNA) from body fluids, cells, or tissues. kit for extracting the nucleic acid, fluorescent labeling material, nucleic acid amplification enzyme and culture medium, instruction manual, etc. It can be done.

[0505] The device of the present invention includes the polynucleotide of the present invention described above, a mutant thereof, or or a fragment thereof, is attached to, for example, a solid phase. Examples of solid phase materials are plastic, paper, glass, and silicon. The preferred material for the solid phase is plastic because of its ease of processing. The shape of the phase is arbitrary, and may be, for example, a square, a round, a rectangular, a film, or the like. The device includes, for example, a device for measurement by hybridization technology. Rarely, specifically blotting devices, nucleic acid arrays (e.g., microarrays, DNA Examples include DNA chips, RNA chips, etc.

[0506] Nucleic acid array technology can be used to add functional groups such as L-lysine coating, amino groups, and carboxyl groups as needed. A spotter or arrayer is placed on the surface of a solid phase that has been subjected to surface treatment such as functional group introduction. A method of spotting nucleic acids using a high-density dispenser, in which minute droplets are dispensed from a nozzle onto a piezoelectric element, etc. A method of spraying nucleic acids onto a solid phase using an inkjet that sprays nucleic acids from a nozzle, The nucleic acids are then linked or attached one by one using a method such as nucleotide synthesis. By this method, an array such as a chip is produced, and the array is used for hybridization. This is a technology for measuring target nucleic acids using

[0507] The kit or device of the present invention is a method for detecting a small amount of miRNA, which is a pancreatic cancer marker in Group 1. At least one, preferably at least two, more preferably at least three and most preferably at least five or more polynucleotides specific to each of the polynucleotides. The kit or device of the present invention further optionally comprises a nucleic acid capable of binding to the above group. At least one or more miRNAs that are pancreatic cancer markers, preferably at least two more preferably at least three or more, and most preferably at least five or more The nucleic acid may contain nucleic acids capable of specifically binding to each of all polynucleotides. The disclosed kit or device may further optionally comprise a marker for pancreatic cancer, m, of Group 3 above. At least one, preferably at least two, more preferably at least two iRNAs At least three or more, most preferably at least five or more, up to all of the polynucleotides The nucleic acid may contain nucleic acids capable of specifically binding to each of the nucleic acids.

[0508] The kit or device of the present invention can be used for the detection of pancreatic cancer according to the following four methods. do.

[0509] 4. Methods for detecting pancreatic cancer The present invention further relates to the kit or device of the present invention (usable in the present invention) described in 3. above. The nucleic acid is selected from the following group and used to detect miR-689 in a sample: 3-5p, miR-6075, miR-6820-5p, miR-4294, miR-6 729-5p, miR-4476, miR-6836-3p, miR-6765-3p, miR-6799-5p, miR-4530, miR-7641, miR-4454, m iR-615-5p、miR-8073、miR-663a、miR-4634、miR -4450、miR-4792、miR-665、miR-7975、miR-7109 -5p、miR-6789-5p、miR-4497、miR-6877-5p、miR -6880-5p、miR-7977、miR-4734、miR-6821-5p、m iR-8089、miR-5585-3p、miR-6085、miR-6845-5p 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-1260 a、miR-6741-5p、miR-6781-5p、miR-6125、miR-6 805-5p、miR-6132、miR-6872-3p、miR-6875-5p、 miR-1908-3p, miR-4433b-3p, miR-4736, miR-51 00、miR-6724-5p、miR-7107-5p、miR-6726-5p、m iR-3185、miR-4638-5p、miR-1273g-3p、miR-677 8-5p、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-4486、miR-1913、 miR-4656、miR-1260b、miR-7106-5p、miR-6889- 5p、miR-6780b-5p、miR-6090、miR-4534、miR-44 49, miR-5195-3p, miR-1202, miR-4467, miR-651 5-3p, miR-4281, miR-4505, miR-4484, miR-6805 -3p, miR-3135b, miR-3162-5p, miR-6768-5p, mi R-6721-5p, miR-1227-5p, miR-6722-3p, miR-42 86, miR-4746-3p, miR-6727-5p, miR-6816-5p, m iR-4741, miR-4508, miR-940, miR-4327, miR-46 65-3p and miR-718, miR-1203, miR-663b, miR-425 8, miR-4649-5p, miR-4516, miR-3619-3p, miR-6 826-5p, miR-6757-5p, miR-3131, miR-1343-3p, Represented by miR-6775-5p, miR-6813-5p and miR-3940-5p and optionally, a miR selected from the group consisting of: -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-37 The expression levels of pancreatic cancer-derived genes represented by miR-1a-5p and miR-550a-5p, and optionally selected from the group consisting of miR-4417, miR-4707-5p, miR-7847-3p, miR-2861, miR-4513, miR-7111-5 p, miR-6777-5p, miR-7113-3p, miR-4648, miR-3 184-5p, 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-6774-5 p, miR-486-3p, miR-6806-5p, miR-6842-5p, miR -6716-5p, miR-557, miR-4673, miR-4674, miR-4 442, miR-1915-3p, miR-4687-3p, and miR-92b-3p the expression levels of pancreatic cancer-derived genes expressed in one or more of The expression level was measured in vitro, and the results were compared between subjects suspected of having pancreatic cancer and healthy subjects. For blood, serum, plasma, and other samples collected from normal subjects (including non-pancreatic cancer patients), For example, the expression levels of the above genes in the rats are compared with the expression levels of healthy controls. If there is a statistically significant difference in the expression level of the target nucleic acid in the sample, it is determined that the subject has a pancreatic The present invention provides a method for detecting pancreatic cancer, comprising assessing a subject as suffering from pancreatic cancer.

[0510] The method of the present invention enables early cancer diagnosis with high sensitivity and specificity in a minimally invasive manner. This will lead to earlier treatment and improved prognosis, and also facilitate monitoring of disease progression and external This allows for the monitoring of the effectiveness of medical, radiotherapeutic, and chemotherapeutic treatments.

[0511] The method of the present invention for extracting genes derived from pancreatic cancer from samples such as blood, serum, and plasma includes the following steps: , 3D-Gene® RNA extraction reagent from Add the RNA extraction reagent in the 100ml liquid sample kit (Toray Industries, Inc.). It is particularly preferable to use the acid phenol method. Alternatively, the ammonium-phenol-chloroform (AGPC) method may be used. Trizol (registered trademark) (Life Technologies) may also be used. Trizol (Life Technologies) and Isogen (Nippon G Alternatively, the solution may be prepared by adding an RNA extraction reagent containing acidic phenol such as phenol (Ethanol, Japan). Furthermore, kits such as miRNeasy (registered trademark) Mini Kit (Qiagen) The method is not limited to these.

[0512] The present invention also relates to a method for detecting a pancreatic cancer-derived antibody in a specimen from a subject using the kit or device of the present invention. The present invention provides a use for in vitro detection of expression products of miRNA genes.

[0513] In the above-mentioned method of the present invention, the above-mentioned kit or device comprises the above-mentioned Polynucleotides usable in the Used.

[0514] In the detection or (genetic) diagnosis of pancreatic cancer of the present invention, the kit or device of the present invention The polynucleotides contained therein can be used as probes or primers. When using TaqMan ( Registered trademark) MicroRNA Assays, Qiagen's miScript P CR System, etc. can be used, but the method is not limited to these.

[0515] The polynucleotides contained in the kit or device of the present invention can be analyzed by Northern blotting, Northern blot, in situ hybridization, Northern hybridization Hybridization techniques such as ionization and Southern hybridization, and quantification By using known methods to specifically detect specific genes, such as quantitative amplification techniques such as RT-PCR. In the above cases, it can be used as a primer or probe according to standard methods. Depending on the type of detection method used, the body fluids may include blood, serum, plasma, urine, etc. Alternatively, total RNA prepared by the above method from such a body fluid is collected. Furthermore, various polymerase chains including cDNA prepared from the RNA may be used. Oligonucleotides may also be used.

[0516] The kit or device of the present invention is useful for diagnosing pancreatic cancer or detecting the presence or absence of pancreatic cancer. Specifically, the detection of pancreatic cancer using the kit or device is The kit or device is used to test blood, serum, plasma, urine, or other samples from subjects suspected of having the disease. The expression level of the gene detected by the nucleic acid probe or primer contained in the This can be done by detecting the blood of a subject suspected of having pancreatic cancer. , SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 4 in samples such as serum, plasma, and urine. 94 or its complementary sequence, and and a base sequence represented by one or more of SEQ ID NOs: 105 to 122 or a complementary sequence thereof, and optionally a base sequence represented by one or more of SEQ ID NOs: 349 to 383 or a complementary sequence thereof. By a polynucleotide consisting of the sequence (including variants, fragments or derivatives thereof) The expression level of the target miRNA marker to be measured is measured in blood, serum, plasma, urine, etc. of a healthy subject. If there is a statistically significant difference compared to the expression levels in the specimen, the subject is diagnosed with pancreatic cancer. It can be assessed that the patient is suffering from

[0517] The method of the present invention can be used in conjunction with abdominal ultrasound, CT scan, endoscopic retrograde pancreatography, and ultrasound. The method of the present invention can be combined with imaging diagnostic methods such as endoscopy. It is possible to specifically detect pancreatic cancer and to substantially distinguish it from cancers other than pancreatic cancer. In particular, in the case of biliary tract cancer, miRNA markers that are partially common to those in pancreatic cancer can be used. However, the discriminant boundary used in the discriminant equation determines whether the patient is diagnosed with pancreatic cancer or not. This may allow biliary tract cancer to be identified, or may be useful in other diagnostic imaging modalities such as those mentioned above. These cancers can be identified by combining this with other diagnostic methods.

[0518] The kit or device of the present invention is used to detect the presence of an expression product of a gene derived from pancreatic cancer in a sample. The method for detecting whether the expression product of a gene derived from pancreatic cancer is not rare or contains the expression product of a gene derived from pancreatic cancer is The expression level of the target gene contained in the collected body fluids such as blood, serum, plasma, and urine is measured. , one or more polynucleotides selected from the group of polynucleotides of the present invention (mutants, The presence or absence of pancreatic cancer is evaluated by measuring the level of the α-glucan-1-phosphate dehydrogenase (α-glucan-1-phosphate dehydrogenase) using a α-glucan-1-phosphate dehydrogenase (α-glucan-1-phosphate dehydrogenase) or a α-glucan-1-phosphate dehydrogenase (α-glucan-1-phosphate dehydrogenase) using a α-glucan-1-phosphate dehydrogenase (α- Alternatively, the method for detecting pancreatic cancer of the present invention may include detecting a cancer of the pancreas, for example, In cancer patients, when a therapeutic drug is administered to improve the disease, The presence or absence or the degree of improvement can also be evaluated or diagnosed.

[0519] The method of the present invention includes, for example, the following steps (a), (b) and (c): (a) A sample from a subject is subjected to in vitro analysis using a polymerase chain reaction (PCR) in a kit or device of the present invention. contacting the oligonucleotide with (b) measuring the expression level of the target nucleic acid in a sample by using the polynucleotide as a nucleic acid probe or primer; measuring using the same as (c) Based on the results of (b), evaluate the presence or absence of pancreatic cancer (cells) in the subject. Worthwhile steps, may include:

[0520] Specifically, the present invention relates to miR-6893-5p, miR-6075, miR-682 0-5p, miR-4294, miR-6729-5p, miR-4476, miR-6 836-3p, miR-6765-3p, miR-6799-5p, miR-4530, miR-7641, miR-4454, miR-615-5p, miR-8073, mi R-663a, miR-4634, miR-4450, miR-4792, miR-66 5, miR-7975, miR-7109-5p, miR-6789-5p, miR-4 497, miR-6877-5p, miR-6880-5p, miR-7977, miR -4734, miR-6821-5p, miR-8089, miR-5585-3p, m iR-6085, miR-6845-5p, miR-4651, miR-4433-3p , miR-1231, miR-4665-5p, miR-7114-5p, miR-12 38-5p, miR-8069, miR-4732-5p, miR-619-5p, mi R-3622a-5p, miR-1260a, miR-6741-5p, miR-678 1-5p、miR-6125、miR-6805-5p、miR-6132、miR-6 872-3p、miR-6875-5p、miR-1908-3p、miR-4433b -3p、miR-4736、miR-5100、miR-6724-5p、miR-71 07-5p、miR-6726-5p、miR-3185、miR-4638-5p、m iR-1273g-3p、miR-6778-5p、miR-328-5p、miR-3 679-3p、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-1260b、mi R-7106-5p、miR-6889-5p、miR-6780b-5p、miR-6 090、miR-4534、miR-4449、miR-5195-3p、miR-12 02、miR-4467、miR-6515-3p、miR-4281、miR-450 5、miR-4484、miR-6805-3p、miR-3135b、miR-316 2-5p、miR-6768-5p、miR-6721-5p、miR-1227-5p 、miR-6722-3p、miR-4286、miR-4746-3p、miR-67 27-5p、miR-6816-5p、miR-4741、miR-4508、miR- 940, miR-4327, miR-4665-3p, miR-718, miR-12 03、miR-663b、miR-4258、miR-4649-5p、miR-451 6、miR-3619-3p、miR-6826-5p、miR-6757-5p、mi R-3131、miR-1343-3p、miR-6775-5p、miR-6813- At least one selected from miR-3940-5p and miR-3940-5p, preferably at least The nucleic acid capable of specifically binding to two or more polynucleotides is used to detect the polynucleotides in a sample of a subject. The expression level of the target nucleic acid in the target nucleic acid is measured, and the measured expression level is compared with a control of a healthy subject similarly measured. The expression level is used to determine whether the subject has pancreatic cancer or not. The present invention provides a method for detecting pancreatic cancer, comprising evaluating in vitro whether or not a tumor is present in a pancreatic cancer cell line.

[0521] In this specification, "evaluation" refers to in vitro testing, not to a doctor's judgment. This is evaluation support based on the results of testing.

[0522] As described above, in the method of the present invention, specifically, miR-6893-5p is -miR-6893-5p, and miR-6075 is hsa-miR-6075 , miR-6820-5p is hsa-miR-6820-5p, and miR-4294 is hsa-miR-4294 and miR-6729-5p is hsa-miR-672 9-5p, miR-4476 is hsa-miR-4476, and miR-683 6-3p is hsa-miR-6836-3p, and miR-6765-3p is hsa- miR-6765-3p and miR-6799-5p are hsa-miR-6799- 5p, miR-4530 is hsa-miR-4530, and miR-7641 is hsa-miR-7641 and miR-4454 , miR-615-5p is hsa-miR-615-5p, and miR-8073 is h sa-miR-8073, and miR-663a is hsa-miR-663a; miR-4634 is hsa-miR-4634 and miR-4450 is hsa-mi miR-4450, miR-4792 is hsa-miR-4792, and miR-6 65 is hsa-miR-665 and miR-7975 is hsa-miR-7975 miR-7109-5p is hsa-miR-7109-5p, and miR-67 89-5p is hsa-miR-6789-5p, and miR-4497 is hsa-mi R-4497, miR-6877-5p is hsa-miR-6877-5p , miR-6880-5p is hsa-miR-6880-5p, and miR-7977 is hsa-miR-7977 and miR-4734 is hsa-miR-4734 miR-6821-5p is hsa-miR-6821-5p, and miR-808 9 is hsa-miR-8089, and miR-5585-3p is hsa-miR-55 85-3p, miR-6085 is hsa-miR-6085, and miR-68 45-5p is hsa-miR-6845-5p, and miR-4651 is hsa-mi R-4651, miR-4433-3p is hsa-miR-4433-3p , miR-1231 is hsa-miR-1231, and miR-4665-5p is hs a-miR-4665-5p and miR-7114-5p are hsa-miR-711 4-5p, miR-1238-5p is hsa-miR-1238-5p, and m iR-8069 is hsa-miR-8069, and miR-4732-5p is hsa- miR-4732-5p and miR-619-5p are hsa-miR-619-5p and miR-3622a-5p is hsa-miR-3622a-5p, and miR -1260a is hsa-miR-1260a, and miR-6741-5p is hsa- miR-6741-5p and miR-6781-5p are hsa-miR-6781- 5p, miR-6125 is hsa-miR-6125, and miR-6805- 5p is hsa-miR-6805-5p, and miR-6132 is hsa-miR-6 132, miR-6872-3p is hsa-miR-6872-3p, and mi R-6875-5p is hsa-miR-6875-5p, and miR-1908-3p is hsa-miR-1908-3p, and miR-4433b-3p is hsa-miR -4433b-3p, miR-4736 is hsa-miR-4736, and mi R-5100 is hsa-miR-5100, and miR-6724-5p is hsa-m iR-6724-5p and miR-7107-5p are hsa-miR-7107-5 p, miR-6726-5p is hsa-miR-6726-5p, and miR- 3185 is hsa-miR-3185 and miR-4638-5p is hsa-miR -4638-5p, and miR-1273g-3p is hsa-miR-1273g-3 p, miR-6778-5p is hsa-miR-6778-5p, and miR- 328-5p is hsa-miR-328-5p, and miR-3679-3p is hsa -miR-3679-3p, and miR-1228-3p is hsa-miR-1228 -3p, miR-6779-5p is hsa-miR-6779-5p, and mi R-4723-5p is hsa-miR-4723-5p, and miR-6850-5p is hsa-miR-6850-5p and miR-760 is hsa-miR-760 miR-7704 is hsa-miR-7704 and miR-8072 is hsa -miR-8072, miR-4486 is hsa-miR-4486, mi R-1913 is hsa-miR-1913, and miR-4656 is hsa-miR- 4656, miR-1260b is hsa-miR-1260b, and miR-7 106-5p is hsa-miR-7106-5p, and miR-6889-5p is hs a-miR-6889-5p and miR-6780b-5p are hsa-miR-67 80b-5p, miR-6090 is hsa-miR-6090, and miR-4 534 is hsa-miR-4534 and miR-4449 is hsa-miR-444 9, miR-5195-3p is hsa-miR-5195-3p, and miR- 1202 is hsa-miR-1202 and miR-4467 is hsa-miR-44 67, miR-6515-3p is hsa-miR-6515-3p, and miR -4281 is hsa-miR-4281, and miR-4505 is hsa-miR-4 505, miR-4484 is hsa-miR-4484, and miR-6805 -3p is hsa-miR-6805-3p, and miR-3135b is hsa-miR -3135b, and miR-3162-5p is hsa-miR-3162-5p , miR-6768-5p is hsa-miR-6768-5p, and miR-6721 -5p is hsa-miR-6721-5p, and miR-1227-5p is hsa-m iR-1227-5p and miR-6722-3p are hsa-miR-6722-3 p, miR-4286 is hsa-miR-4286, and miR-4746-3 p is hsa-miR-4746-3p and miR-6727-5p is hsa-miR -6727-5p, and miR-6816-5p is hsa-miR-6816-5p miR-4741 is hsa-miR-4741 and miR-4508 is hsa -miR-4508, miR-940 is hsa-miR-940, and miR- 4327 is hsa-miR-4327, and miR-4665-3p is hsa-miR -4665-3p, and miR-718 is hsa-miR-718, and mi R-1203 is hsa-miR-1203, and miR-663b is hsa-miR- 663b, miR-4258 is hsa-miR-4258, and miR-464 9-5p is hsa-miR-4649-5p, and miR-4516 is hsa-miR -4516, and miR-3619-3p is hsa-miR-3619-3p; miR-6826-5p is hsa-miR-6826-5p, and miR-6757- 5p is hsa-miR-6757-5p, and miR-3131 is hsa-miR-3 131, and miR-1343-3p is hsa-miR-1343-3p , miR-6775-5p is hsa-miR-6775-5p, and miR-6813 -5p is hsa-miR-6813-5p, and miR-3940-5p is hs a-miR-3940-5p.

[0523] In the method of the present invention, specifically, nucleic acids (specifically, probes or primers) -) is a polynucleotide shown in any one of (a) to (e) below: (a) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A polynucleotide consisting of a base sequence, or a base sequence in which u is t a nucleotide sequence of 15 or more consecutive bases, a variant thereof, a derivative thereof, or a fragment thereof, (b) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 a polynucleotide comprising a base sequence; (c) Represented by any of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A base sequence complementary to the base sequence, or the base sequence in which u is replaced by t a polynucleotide comprising 15 or more consecutive bases, a variant thereof, a derivative thereof, or The fragment, (d) a sequence represented by any one of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 A base sequence complementary to the base sequence, or the base sequence in which u is t, a polynucleotide comprising: (e) A polynucleotide that binds to any one of the polynucleotides (a) to (d) under stringent conditions. hybridizing polynucleotides, is selected from the group consisting of:

[0524] The nucleic acid in the method of the present invention may further comprise miR-125a-3p, miR-204-3 p, miR-1469, miR-575, miR-150-3p, miR-423-5p , miR-564, miR-3188, miR-1246, miR-602, miR-1 290, miR-16-5p, miR-451a, miR-24-3p, miR-187 -5p, miR-1908-5p, miR-371a-5p and miR-550a-5p The nucleic acid comprises a nucleic acid capable of specifically binding to at least one polynucleotide selected from It is possible.

[0525] Specifically, miR-125a-3p is hsa-miR-125a-3p, and mi R-204-3p is hsa-miR-204-3p, and miR-1469 is hsa- miR-1469, miR-575 is hsa-miR-575, and miR-1 50-3p is hsa-miR-150-3p, and miR-423-5p is hsa-m iR-423-5p, miR-564 is hsa-miR-564, and miR- 3188 is hsa-miR-3188 and miR-1246 is hsa-miR-12 46, miR-602 is hsa-miR-602, and miR-1290 is hs a-miR-1290, miR-16-5p is hsa-miR-16-5p , miR-451a is hsa-miR-451a, and miR-24-3p is hsa- miR-24-3p and miR-187-5p are hsa-miR-187-5p. miR-1908-5p is hsa-miR-1908-5p, and miR-371 a-5p is hsa-miR-371a-5p, and miR-550a-5p is h sa-miR-550a-5p.

[0526] More specifically, the nucleic acid is a polynucleotide shown in any one of (f) to (j) below: Do: (f) a base sequence represented by any one of SEQ ID NOs: 105 to 122, or the base sequence a polynucleotide consisting of the base sequence in which u is t, a variant thereof, a derivative thereof, or is a fragment containing 15 or more consecutive bases, (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 105 to 122; (h) a base sequence represented by any one of SEQ ID NOs: 105 to 122, or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, and a variant thereof a fragment thereof containing 15 or more consecutive bases, (i) a base sequence represented by any one of SEQ ID NOs: 105 to 122, or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; and (j) A method for detecting a polynucleotide that is hybridized with any one of the polynucleotides (f) to (i) under stringent conditions. hybridizing polynucleotides, is selected from the group consisting of:

[0527] The nucleic acid also contains miR-4417, miR-4707-5p, and miR-7847-3 p, 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-7108-5 p, 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 iR-557, miR-4673, miR-4674, miR-4442, miR-19 At least one selected from miR-15-3p, miR-4687-3p, and miR-92b-3p The nucleic acid may also comprise a nucleic acid capable of specifically binding to one or more polynucleotides.

[0528] Specifically, miR-4417 is hsa-miR-4417 and miR-4707 -5p is hsa-miR-4707-5p, and miR-7847-3p is hsa-m iR-7847-3p, miR-2861 is hsa-miR-2861, and m iR-4513 is hsa-miR-4513, and miR-7111-5p is hsa- miR-7111-5p and miR-6777-5p are hsa-miR-6777- 5p, miR-7113-3p is hsa-miR-7113-3p, and miR -4648 is hsa-miR-4648, and miR-3184-5p is hsa-mi miR-3184-5p, miR-4271 is hsa-miR-4271, and mi R-6791-5p is hsa-miR-6791-5p, and miR-642a-3p is hsa-miR-642a-3p, and miR-7108-5p is hsa-miR- 7108-5p, and miR-128-1-5p is hsa-miR-128-1-5p , miR-5196-5p is hsa-miR-5196-5p, and miR-3 178 is hsa-miR-3178, and miR-3656 is hsa-miR-365 6, miR-92a-2-5p is hsa-miR-92a-2-5p, and mi R-6769b-5p is hsa-miR-6769b-5p, and miR-4689 is hsa-miR-4689 and miR-6076 , miR-92b-5p is hsa-miR-92b-5p, and miR-6774-5 p is hsa-miR-6774-5p, and miR-486-3p is hsa-miR- 486-3p, and miR-6806-5p is hsa-miR-6806-5p , miR-6842-5p is hsa-miR-6842-5p, and miR-6716 -5p is hsa-miR-6716-5p, and miR-557 is hsa-miR-5 57, miR-4673 is hsa-miR-4673, and miR-4674 is hsa-miR-4674 and miR-4442 , miR-1915-3p is hsa-miR-1915-3p, and miR-4687 -3p is hsa-miR-4687-3p, and miR-92b-3p is hsa -miR-92b-3p.

[0529] More specifically, the nucleic acid is a polynucleotide shown in any one of (k) to (o) below: Do: (k) a base sequence represented by any one of SEQ ID NOs: 349 to 383, or the base sequence a polynucleotide consisting of the base sequence in which u is t, a variant thereof, a derivative thereof, or is a fragment containing 15 or more consecutive bases, (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 349 to 383; (m) a base sequence represented by any one of SEQ ID NOs: 349 to 383, or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, and a variant thereof a fragment thereof containing 15 or more consecutive bases, (n) a base sequence represented by any one of SEQ ID NOs: 349 to 383, or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; and (o) a polynucleotide that binds to any one of the polynucleotides (k) to (n) under stringent conditions; hybridizing polynucleotides, The polynucleotide is selected from the group consisting of:

[0530] The specimen used in the method of the present invention may be a biological tissue (preferably pancreatic tissue), blood, Examples of specimens include those prepared from body fluids such as serum, plasma, and urine. RNA-containing samples prepared from the tissue, and polynucleotides further prepared from the samples Samples containing blood, serum, plasma, urine, and other bodily fluids, or a part or all of a subject's biological tissue, These are samples taken by a microscope or extracted by surgery, and measurements are taken from these samples. A specimen can be prepared for the following:

[0531] As used herein, a subject refers to a mammal, including but not limited to a human, a primate such as a monkey, a mouse, This refers to rodents such as rats, pets such as dogs and cats, and sport animals such as horses. , preferably human.

[0532] In the method of the present invention, the steps can be changed depending on the type of specimen to be measured. can.

[0533] When RNA is used as the measurement target, the detection of pancreatic cancer (cells) can be performed using, for example, the following steps: Steps (a), (b) and (c): (a) RNA prepared from a subject's sample or a complementary polynucleotide transcribed therefrom; The sequence for combining the cDNA with the polynucleotide in the kit or device of the present invention is Tep, (b) RNA derived from the sample or synthesized from the RNA bound to the polynucleotide The cDNA thus obtained is subjected to hybridization using the polynucleotide as a nucleic acid probe. or quantitative RT-PCR using the above polynucleotides as primers. measuring by R, (c) Based on the results of the measurement in (b) above, the presence or absence of pancreatic cancer (or the expression of a gene derived from pancreatic cancer) Evaluating absence; may include:

[0534] This invention allows for the in vitro detection, testing, and evaluation of pancreatic cancer (or its resulting gene expression). For example, various hybridization techniques can be used to evaluate or diagnose Such hybridization methods include, for example, Northern blotting and Southern blotting. PCR method, RT-PCR method, DNA chip analysis method, in situ hybridization method , Northern hybridization, Southern hybridization, etc. It is possible.

[0535] When using the Northern blot method, the above-mentioned nucleic acid probes that can be used in the present invention are used. By doing so, it is possible to detect and measure the presence or absence of expression of each gene in RNA and its expression level. Specifically, the nucleic acid probe (complementary strand) is irradiated with a radioisotope ( 32 P, 33 P, 35 S Label with a fluorescent substance or the like, and transfer it to a nylon membrane or the like according to the usual method. After hybridization with RNA from the tissue of the subject, the D The signal derived from the label (radioisotope or fluorescent substance) of the NA / RNA duplex is emitted. X-ray detector (BAS-1800II (Fuji Photo Film Co., Ltd., Japan)) or a fluorescence detector (STORM 865 (GE Healthcare), etc.) Examples of methods for detecting and measuring include the following.

[0536] When quantitative RT-PCR is used, the above primers that can be used in the present invention are used. This makes it possible to detect or measure the presence or absence of gene expression in RNA and the amount of expression. Specifically, cDNA can be prepared from RNA derived from the biological tissue of a subject according to a conventional method. The detection composition of the present invention is prepared so that the region of each target gene can be amplified using the prepared template. A pair of primers (consisting of a positive strand and a reverse strand that bind to the above cDNA) prepared from the above composition was used. The resulting double-stranded DNA is detected by hybridizing it with DNA and performing PCR using standard methods. As a method for detecting double-stranded DNA, the above-mentioned PCR method can be exemplified. A method using primers that have been labeled with radioisotopes or fluorescent substances in advance, P The CR product is electrophoresed on an agarose gel, and the double-stranded DNA is stained with ethidium bromide or the like. The double-stranded DNA produced is detected by colorimetry, and the resulting double-stranded DNA is then transferred to a nylon membrane or other suitable membrane in the usual manner. The method involves transferring the DNA to a substrate, hybridizing it with a labeled nucleic acid probe, and detecting it. It can include.

[0537] When nucleic acid array analysis is used, the detection composition of the present invention is used as a nucleic acid probe (single-stranded An RNA chip or DNA chip attached to a substrate (solid phase) is used as a double-stranded or double-stranded probe. The area where the nucleic acid probe is attached is called a probe spot, and the area where the nucleic acid probe is not attached is called a probe spot. The region where the gene cluster is immobilized on the substrate is generally called a nucleic acid chip. They are called arrays, nucleic acid arrays, microarrays, etc., and are based on DNA or RNA arrays. includes DNA or RNA macroarrays and DNA or RNA microarrays. However, in this specification, when we say "chip," we mean the array. The 3D-Gene (registered trademark) Human miRNA Oligo chip (Tohoku University) Although the company (Re Corporation) can be used, it is not limited to this.

[0538] The measurement of the DNA chip is not limited to, but may be performed by, for example, detecting a signal derived from a label of the detection composition. Null was detected by an image detector (Typhoon 9410 (GE Healthcare)), 3D-Gene ( Examples of methods for detecting and measuring include a scanner (registered trademark) (Toray Industries, Inc.) It is possible.

[0539] As used herein, "stringent conditions" refers to conditions under which the nucleic acid probe is to a detectably greater extent (e.g., background measurements) than for other sequences. (mean + standard error of background measurement × 2 or more measurements) for that target sequence These are hybridization conditions.

[0540] Stringent conditions are defined by hybridization and subsequent washing. The hybridization conditions are not limited, but may be, for example, 30°C to 60°C, Solutions containing SSC, detergents, formamide, dextran sulfate, blocking agents, etc. The conditions are 1 to 24 hours in 1×SSC, which is 150 mM sodium chloride and The aqueous solution (pH 7.0) contained 15 mM sodium citrate and 15 mM SDS as a surfactant. (sodium dodecyl sulfate), Triton, or Tween. The dilution conditions are preferably 3 to 10×SSC, 0.1 to 1% SDS. Another condition that defines stringent conditions is the hybridization The post-treatment washing conditions are, for example, 0.5×SSC and 0.1% SDS at 30°C. solution, and a solution containing 0.2x SSC and 0.1% SDS at 30°C, and a solution containing 0.05 The complementary strand is purified under such conditions as continuous washing with a ×SSC solution. It is desirable that the hybridized state with the target positive strand is maintained even after washing with Specifically, such a complementary strand is a strand that is completely complementary to the base sequence of the target positive strand. and a strand consisting of a base sequence comprising at least 80%, preferably at least 85%, of said strand. , more preferably at least 90% or at least 95%, for example at least 98% or An example is a chain consisting of base sequences that share at least 99% identity.

[0541] Other examples of "stringent conditions" for these hybridizations are See, for example, Sambrook, J. & Russell, D., Molecules lar Cloning, A LABORATORY MANUAL, Cold Sp Ring Harbor Laboratory Press, January 15, 2001 This is described in Vol. 1, 7.42-7.45, Vol. 2, 8.9-8.17, etc. Available in Ming.

[0542] Conditions for carrying out PCR using the polynucleotide fragments of the kit of the present invention as primers Examples of the buffer include 10 mM Tris-HCl (pH 8.3), 50 mM KCL, Using a PCR buffer with a composition of 1-2mM MgCl2, etc., Examples include treating the sample at a temperature of +5 to +10°C (calculated Tm) for 15 seconds to 1 minute. The Tm value can be calculated as follows: Tm value = 2 × (number of adenine residues + number of thymine residues) + Examples include 4 × (number of guanine residues + number of cytosine residues).

[0543] When quantitative RT-PCR is used, TaqMan (registered trademark) Micro RNA Assays (Life Technologies), LNA (registered trademark) -based MicroRNA PCR (Exiqon), Ncode (registered trademark) miRNA, such as miRNA qRT-PCT kit (Invitrogen) A commercially available measurement kit specially designed for quantitative measurement may also be used.

[0544] The gene expression level can be calculated by, but not limited to, statistical and alysis of gene expression microarray dat a (Speed T., Chapman and Hall / CRC), and A be ginner's guide Microarray gene expression n data analysis(Causton HC et al., Blackwell Statistical processing described in, for example, the US Pat. No. 6,299,499 B2, can be used in the present invention. For example, the average value of the measurements of the blank spots on the DNA chip is added to the measurement of the blank spots. Add two times, preferably three times, and more preferably six times the standard deviation of the fixed value, and add the value above that. The probe spots having a signal value can be considered as detection spots. The average value of the ink spot measurements was considered as the background, and the average value of the probe spot measurements was The gene expression level can be calculated by subtracting from the missing value of the gene expression level. Either exclude them from the target or, preferably, replace them with the minimum gene expression level on each DNA chip. or, more preferably, by the logarithm of the minimum gene expression level minus 0.1. Furthermore, to eliminate genes with low signals, 20% of the measurement samples were used. % or more, preferably 50% or more, more preferably 80% or more, Only genes with gene expression levels of 2 to the power of 8, or more preferably 2 to the power of 10, are analyzed. As a normalization of gene expression levels, are, but are not limited to, global normalization and quantitative le normalization (Bolstad, BM et al., 2003, B ioinformatics, Vol. 19, pp. 185-193).

[0545] The present invention also relates to diagnostic polynucleotides, kits, devices (e.g., chips) of the present invention. or a combination thereof to measure the expression of a target gene or genes in a sample from a subject. The gene expression levels of samples from pancreatic cancer patients and healthy subjects were measured and compared with the teacher sample. A discriminant (discriminant function) was created as follows, and the sample contained a gene derived from pancreatic cancer and / or Provide a method for determining or assessing non-inclusion.

[0546] That is, the present invention further provides the diagnostic polynucleotides, kits, devices (e.g., For example, a chip) or a combination thereof can be used to confirm that the sample contains genes derived from pancreatic cancer. and / or multiple tests known to determine or assess the absence of genes derived from pancreatic cancer. A first step is to measure the expression level of a target gene in a living body in vitro. A discriminant equation is created using the measured expression level of the target gene obtained in step 1 as a training sample. In the second step, the expression level of the target gene in a sample derived from a subject is measured in the same manner as in the first step. The third step is to measure in vitro in the same way as above, and the discriminant obtained in the second step is Substitute the measured value of the expression level of the target gene obtained in the third step into Based on the results obtained, it is determined that the sample contains a gene derived from pancreatic cancer and / or that the pancreas a fourth step of determining or assessing that the sample does not contain a gene derived from cancer, The target gene is a polynucleotide, a polynucleotide contained in a kit or a device (e.g., a chip). the method, which is detectable by a nucleotide, a variant thereof, or a fragment thereof. Here, we provide Fisher's discriminant analysis and nonlinear discriminant analysis using Mahalanobis distance. , neural network, Support Vector Machine (SVM) The discriminant can be created using, but is not limited to, the following.

[0547] In linear discriminant analysis, when the boundary between groups is a straight line or a hyperplane, Equation 1 is used as the discriminant. Here, x is the explanatory variable, w is the coefficient of the explanatory variable, and w0 is a constant term.

[0548]

number

[0549] The value obtained from the discriminant equation is called the discriminant score, and it explains the measurements of a newly given data set. The discriminant score is substituted as a variable into the discriminant equation, and the grouping can be determined by the sign of the discriminant score.

[0550] Fisher's discriminant analysis, a type of linear discriminant analysis, is a dimensional analysis suitable for classifying It is a dimension reduction method for selecting data with the same label by focusing on the variance of synthetic variables. By minimizing the variance of the data, a highly discriminative composite variable is constructed (Venables, W. Modern Applied Statistics with S. Fourth edition. Springer, 2002). Fisher's In discriminant analysis, we find the projection direction w that maximizes Equation 2. Here, μ is the mean of the input, n g is the number of data belonging to class g, and μg is the average of the input data belonging to class g. The numerator and denominator are the between-class variance and the within-class variance when the data is projected in the direction of vector w, respectively. The discriminant coefficient wi is calculated by maximizing this ratio. (Kanamori Takafumi et al. , "Pattern Recognition", Kyoritsu Shuppan, Tokyo, Japan (2009), Richard O. et al. Author, Pattern Classification Second Edition. , Wiley-Interscience, 2000).

[0551]

number

[0552] The Mahalanobis distance was calculated using Equation 3, which takes into account the correlation of the data. It can be used as a nonlinear discriminant analysis to distinguish groups that are close to each other as belonging groups. , μ is the center vector of each group, and S-1 is the inverse matrix of the variance-covariance matrix of that group. The torque is calculated from the explanatory variable x, and the mean vector or median vector can be used. do.

[0553]

number

[0554] SVM is a discriminant analysis method invented by V. Vapnik (The Nature f Statistical Leaning Theory, Springer, 19 95). Specific data items in a data set with known classification groups are used as explanatory variables and classification variables. To correctly classify the dataset into known groups using the target group as the objective variable A boundary surface called a hyperplane is determined, and a discriminant formula for classifying the data is determined using the boundary surface. The discriminant is then assigned the measurements of the newly given data set as explanatory variables. By substituting the value into the discriminant, the grouping can be determined. The result may be the group to be classified, or the probability of being classified into the group to be classified. Distance is also acceptable. In SVM, feature vectors are highly refined as a way to deal with nonlinear problems. A method is known in which a nonlinear transformation is performed to a dimension and a linear discrimination is performed in that space. An expression in which the dot product of two elements in the given space is expressed only in terms of the inputs in the original space. The kernel is called a kernel, and examples of kernels are the linear kernel and RBF (Radial Basis Function). Basis Function kernel and Gaussian kernel. While mapping to a higher dimension using a kernel, we actually avoid computing features in the mapped space. Therefore, it is possible to construct an optimal discriminant, i.e., a discriminant, by calculating only the kernel (for example, For example, Hideki Aso et al., Frontiers of Statistical Science 6, "Statistics of Pattern Recognition and Learning: A New Concept" "Thoughts and Methods", Iwanami Shoten, Tokyo, Japan (2004), Nello Cristiani ni et al., Introduction to SVM, Kyoritsu Shuppan, Tokyo, Japan (2008).

[0555] C-support vector classification, a type of SVM method on(C-SVC) is a method that creates a hyperplane by learning with two groups of explanatory variables and then applies it to unknown data sets. (C. Cortes et al., 1995, Ma Chine Learning, Vol. 20, p273-297).

[0556] An example of calculating a discriminant for C-SVC that can be used in the method of the present invention is shown below. The subjects are divided into two groups: pancreatic cancer patients and healthy subjects. The standard for determining whether a disease is a pancreatic disease can be, for example, a pancreatic tissue test.

[0557] Next, a dataset consisting of comprehensive gene expression levels of the two separated serum samples ( We prepared a group of samples (hereinafter referred to as the learning sample group) and identified genes that showed clear differences in gene expression levels between the two groups. The discriminant equation using C-SVC with the explanatory variables and the grouping as the objective variable (for example, -1 and +1) Equation 4 is the objective function to be optimized, where e is the total input vector, and y is The objective variable is a vector of Lagrange multipliers, Q is a positive definite matrix, and C is a matrix used to adjust the constraints. Represents the parameter to be adjusted.

[0558]

number

[0559] Equation 5 is the final discriminant, and the sign of the value obtained by the discriminant indicates the group to which it belongs. where x is the support vector, y is the label indicating the group, and a is the corresponding is the coefficient, b is a constant term, and K is the kernel function.

[0560]

number

[0561] As the kernel function, for example, the RBF kernel defined by Equation 6 can be used. where x is the support vector and γ is the kernel parameter that adjusts the complexity of the hyperplane. vinegar.

[0562]

number

[0563] In addition to these, the specimen from the subject contains expression of target genes derived from pancreatic cancer. and / or determine or evaluate the absence or presence of the protein, or compare the expression level with a control derived from a healthy subject. As methods for evaluating the data, neural networks, k-nearest neighbors, decision trees, and logistic regressions are used. You can choose a method such as regression analysis.

[0564] The method of the present invention may, for example, comprise the following steps (a), (b) and (c): (a) Tissue containing a pancreatic cancer-derived gene derived from a pancreatic cancer patient and / or a pancreas derived from a healthy subject Expression of target genes in tissues already known to contain cancer-derived genes The amount of the polynucleotide, kit or device (e.g., DNA chip) for detection according to the present invention ) measuring the (b) From the measured expression levels measured in (a), the discriminants of the above formulas 1 to 3, 5 and 6 are calculated. Steps to create, (c) The expression level of the target gene in a sample derived from a subject is measured using a diagnostic (detection) method according to the present invention. (b) measuring using a polynucleotide, kit, or device (e.g., a DNA chip); Based on the results obtained, the specimen was determined to be a target of pancreatic cancer. Determine or assess the presence and / or absence of expression of a target gene or assessing the amount of the protein expressed by the antibody in comparison with a control derived from a healthy subject; may include:

[0565] Here, x in Equations 1 to 3, 5 and 6 is an explanatory variable, and is the polynomial described in Section 2 above. The method is carried out by measuring a polynucleotide selected from nucleotides or a fragment thereof. Specifically, the explanatory variables for discriminating between pancreatic cancer patients and healthy subjects in the present invention include the following values: For example, the gene expression level is selected from any one of the following (1) to (3).

[0566] (1) Represented by any of SEQ ID NOs: 1 to 104, 464 to 473, and 492 to 494 In the base sequence or its complementary sequence, 15 or more consecutive bases or Pancreatic cancer measured by either RNA or DNA containing the base u = t Gene expression levels in serum of patients or healthy individuals.

[0567] (2) A base sequence represented by any one of SEQ ID NOs: 105 to 122 or its complementary sequence RNA containing 15 or more consecutive bases or a base in which the u of the base is t is also in the serum of pancreatic cancer patients or healthy subjects measured either by ELISA or DNA. Gene expression levels.

[0568] (3) A base sequence represented by any one of SEQ ID NOs: 349 to 383 or its complementary sequence RNA containing 15 or more consecutive bases or a base in which the u of the base is t is also in the serum of pancreatic cancer patients or healthy subjects measured either by ELISA or DNA. Gene expression levels.

[0569] As described above, it is possible to detect whether a sample derived from a subject contains and / or contains a gene derived from pancreatic cancer. As a method for determining or evaluating whether or not a discriminant is present, a discriminant is created using a training sample group. A discriminant is required, and in order to improve the discrimination accuracy of the discriminant, It is necessary to use genes with clear differences in the discriminant.

[0570] Furthermore, it is preferable to determine the genes to be used as explanatory variables in the discriminant equation as follows. First, we compared the comprehensive gene expression levels of the pancreatic cancer patient group and the healthy control group, which are the training sample groups. The expression level was used as a data set, and the P value of the t-test, which is a parametric analysis, and the P value of the non-parametric The P value of the Mann-Whitney U test, which is a risk analysis, or the P value of the Wilcoxon test The magnitude of the difference in expression level of each gene between the two groups is calculated using values such as the expression level of each gene.

[0571] The risk rate (significance level) of the P value obtained by the test is, for example, 5%, 1%, or 0.01%. A difference smaller than the mean can be considered statistically significant.

[0572] To correct for the increased probability of type I error due to repeated testing, Correction can be performed by methods such as Bonferroni and Holm (e.g. , Yasushi Nagata et al., "Basics of Statistical Multiple Comparison Methods", Scientist Publishing (2007). For example, the P value obtained by a test is multiplied by the number of times the test is repeated. , i.e., multiplied by the number of genes used in the analysis and compared to the desired significance level to obtain the overall This can reduce the probability of making a type I error.

[0573] In addition, rather than testing, the gene expression levels of the pancreatic cancer patient group and the healthy control group were compared. The absolute value (fold change) of the expression ratio of the median expression level of each gene was calculated and judged. Genes to be used as explanatory variables in a separate formula may also be selected. A ROC curve was created using gene expression levels, and the AUROC value was used as the explanatory variable for the discriminant equation. The gene to be used may be selected.

[0574] Next, using an arbitrary number of genes with large differences in gene expression levels obtained here, A discriminant that can be calculated using the method above is created. A discriminant that obtains the maximum discriminant accuracy is constructed. For example, we can use the P-value significance level to find a discriminant for every combination of genes. The method of construction and the genes used to create the discriminant equation are selected based on the gene expression level with large differences. There are methods for repeatedly evaluating the number of items by increasing it one by one (Furey TS. et al., (2000, Bioinformatics., Vol. 16, p906-14). This discriminant In contrast, the gene expression levels of other independent pancreatic cancer patients or healthy individuals were substituted as explanatory variables, The discrimination results for the group to which these independent pancreatic cancer patients or healthy subjects belong are calculated. That is, the diagnostic gene set found and the discriminant constructed using the diagnostic gene set are By evaluating a group of independent specimens, a diagnostic method that can detect more common pancreatic cancers may be developed. A gene set and a method for discriminating pancreatic cancer can be found.

[0575] In addition, the discriminant performance (generalizability) of the discriminant was evaluated using the split-sample method. That is, it is preferable to divide the dataset into a training sample group and a test sample group, and Gene selection and discriminant formula creation are performed using statistical tests on a group of training samples, and test samples are analyzed using the discriminant formula. Accuracy, sensitivity, and specificity were calculated using the results of group discrimination and the true group to which the test sample group belonged. , and evaluate the discrimination performance. On the other hand, statistical tests are performed using all samples without dividing the dataset. The gene is selected and a discriminant formula is created, and a newly prepared sample is discriminated using the discriminant formula to check the accuracy. Sensitivity and specificity can also be calculated to evaluate discriminant performance.

[0576] The present invention relates to a disease diagnostic polynucleotide useful for the diagnosis and treatment of pancreatic cancer, Method for detecting pancreatic cancer using a polynucleotide, and method for detecting pancreatic cancer containing the polynucleotide We provide a kit and device for detecting tumors, especially those related to the existing tumor markers CEA and CA19-9. In order to select diagnostic genes and create a discriminant formula that show accuracy excee...

Claims

1. A kit for detecting pancreatic cancer, comprising one or more nucleic acids capable of specifically binding to a polynucleotide of miR-4736, a pancreatic cancer marker.

2. The kit according to claim 1, wherein the nucleic acid is at least one polynucleotide or a fragment thereof selected from the group consisting of the following polynucleotides (a) to (e) or fragments thereof: (a) (1) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is replaced with t, or a fragment thereof containing 15 or more consecutive bases; (2) A polynucleotide containing one or two base deletions, substitutions, additions, or insertions in the base sequence of the polynucleotide of (1), or (3) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (1), (b) a polynucleotide containing the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (c) (4) A polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (5) A polynucleotide containing a deletion, substitution, addition, or insertion of one or two bases in the base sequence of the polynucleotide of (4), or (6) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (4). (d) a polynucleotide containing a base sequence complementary to the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; and (e) A polynucleotide that hybridizes with any one of the polynucleotides (a) to (d) under highly stringent conditions.

3. The kit includes other pancreatic cancer markers, namely miR-6893-5p, miR-6075, miR-6820-5p, miR-4294, miR-6729-5p, miR-4476, miR-6765-3p, miR-6799-5p, miR-4530, miR-7641, miR-4454, miR-615-5p, miR-8073, miR-663a, miR-4634, miR-4450, miR-4792, miR-665, 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, miR-6845-5p, 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-6875-5p, miR-1908-3p, miR-4433b-3p, miR-5100, miR-6724-5p, miR-7107-5p, miR-6726-5p, miR-3185, miR-4638-5p, miR-1273g-3p, miR-6778-5p, 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-1913, miR-4656, miR-1260b, miR-7106-5p, miR-6889-5p, miR-6780b-5p, 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-3162-5p, miR-6768-5p, miR-6721-5p, miR-1227-5p, miR-6722-3p, miR-4286miR-4746-3p, miR-6727-5p, miR-6816-5p, miR-4741, miR-4508, miR-9 40, 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-6757-5p, mi R-3131, miR-1343-3p, miR-6775-5p, miR-6813-5p and miR-3940-5p, and / Or miR-125a-3p, miR-204-3p, miR-1469, miR-575, miR-150-3p, miR-4 23-5p, miR-564, miR-3188, miR-1246, miR-602, miR-1290, miR-16-5p, m iR-451a, miR-24-3p, miR-187-5p, miR-1908-5p, miR-371a-5p, miR-55 0a-5p, 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-4 271, miR-6791-5p, miR-642a-3p, miR-7108-5p, miR-128-1-5p, miR-51 96-5p, 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-6 The kit according to claim 1 or 2, further comprising one or more nucleic acids capable of specifically binding to one or more polynucleotides selected from the group consisting of miR-665 and miR-8072, miR-842-5p, miR-6716-5p, miR-557, miR-4673, miR-4674, miR-4442, miR-1915-3p, miR-4687-3p, and miR-92b-3p (excluding a combination of polynucleotides comprising miR-665 and miR-8072 and a combination of polynucleotides comprising miR-4665-5p and miR-1469).

4. The kit according to claim 3, wherein the nucleic acid is at least one polynucleotide or a fragment thereof selected from the group consisting of the polynucleotides (f) to (j) below or fragments thereof: (f) (7) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or a base sequence in which u is t in the base sequence, or a fragment thereof containing 15 or more consecutive bases; (8) A polynucleotide comprising the deletion, substitution, addition, or insertion of one or two bases in the base sequence of the polynucleotide of (7), or (9) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (7). (g) a polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or a base sequence in which u is t in the base sequence, or a fragment thereof containing 15 or more consecutive bases; (h) (10) A polynucleotide consisting of a base sequence complementary to any of SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (11) A polynucleotide comprising the base sequence of the polynucleotide of (10) above, which has one or two base deletions, substitutions, additions, or insertions; or (12) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (10). (i) A polynucleotide containing a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (j) A polynucleotide that hybridizes under highly stringent conditions with any one of the polynucleotides (f) to (i).

5. A device for detecting pancreatic cancer, comprising one or more nucleic acids capable of specifically binding to a polynucleotide of miR-4736, a pancreatic cancer marker.

6. The device according to claim 5, wherein the nucleic acid is at least one polynucleotide or a fragment thereof selected from the group consisting of the polynucleotides (a) to (e) below or fragments thereof: (a) (13) A polynucleotide consisting of the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (14) A polynucleotide comprising the deletion, substitution, addition, or insertion of one or two bases in the base sequence of the polynucleotide of (13), or (15) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (13). (b) a polynucleotide containing the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (c) (16) A polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (17) A polynucleotide comprising the base sequence of the polynucleotide of (16) above, which has one or two base deletions, substitutions, additions, or insertions; or (18) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (16). (d) a polynucleotide containing a base sequence complementary to the base sequence represented by SEQ ID NO: 53 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; and (e) A polynucleotide that hybridizes with any one of the polynucleotides (a) to (d) under highly stringent conditions.

7. The device is another pancreatic cancer marker, miR-6893-5p, miR-6075, miR-6820-5p, miR-4294, miR-6729-5p, miR-4476, miR-6765-3p, miR-6799-5p, miR-4530, miR-7641, miR-4454, miR-615-5p, miR-8073, miR-663a, miR-4634, miR-4450, miR-4792, miR-665, 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, miR-6845-5p, 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-6875-5p, miR-1908-3p, miR-4433b-3p, miR-5100, miR-6724-5p, miR-7107-5p, miR-6726-5p, miR-3185, miR-4638-5p, miR-1273g-3p, miR-6778-5p, 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-1913, miR-4656, miR-1260b, miR-7106-5p, miR-6889-5p, miR-6780b-5p, 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-3162-5p, miR-6768-5p, miR-6721-5p, miR-1227-5p, miR-6722-3pmiR-4286, miR-4746-3p, miR-6727-5p, miR-6816-5p, miR-4741, miR-45 08, miR-940, miR-4327, miR-4665-3p, miR-718, miR-1203, miR-663b, mi R-4258, miR-4649-5p, miR-4516, miR-3619-3p, miR-6826-5p, miR-6757 -5p, miR-3131, miR-1343-3p, miR-6775-5p, miR-6813-5p and miR-3940-5 p, and / or 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, mi R-550a-5p, 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, mi R-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- The device according to claim 5 or 6, further comprising one or more nucleic acids capable of specifically binding to one or more polynucleotides selected from the group consisting of miR-665 and miR-8072, miR-4665-5p, miR-6716-5p, miR-557, miR-4673, miR-4674, miR-4442, miR-1915-3p, miR-4687-3p, and miR-92b-3p (excluding a combination of polynucleotides comprising miR-665 and miR-8072 and a combination of polynucleotides comprising miR-4665-5p and miR-1469).

8. The device according to claim 7, wherein the nucleic acid is at least one polynucleotide or a fragment thereof selected from the group consisting of the polynucleotides (f) to (j) below or fragments thereof: (f) (19) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or a base sequence in which u is t in the base sequence, or a fragment thereof containing 15 or more consecutive bases; (20) A polynucleotide comprising the base sequence of the polynucleotide of (19) above, which has one or two base deletions, substitutions, additions, or insertions; or (21) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (19). (g) a polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or a base sequence in which u is t in the base sequence, or a fragment thereof containing 15 or more consecutive bases; (h) (22) A polynucleotide consisting of a base sequence complementary to any one of SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (23) A polynucleotide comprising the deletion, substitution, addition, or insertion of one or two bases in the base sequence of the polynucleotide of (22), or (24) A polynucleotide showing 90% or more identity with the base sequence of the polynucleotide of (22). (i) A polynucleotide containing a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 1 to 6, 8 to 52, 54 to 70, 72 to 104, 105 to 122, 349 to 383, 464 to 473, and 492 to 494, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (j) A polynucleotide that hybridizes under highly stringent conditions with any one of the polynucleotides (f) to (i).

9. The device according to any one of claims 5 to 8, which is a device for measurement by hybridization technology.

10. The device of claim 9 , wherein the hybridization technology is a nucleic acid array technology.

11. A method for assisting in the detection of pancreatic cancer, comprising measuring the expression level of a target nucleic acid in a specimen from a subject using the kit according to any one of claims 1 to 4 or the device according to any one of claims 5 to 10, and evaluating in vitro whether the subject is affected with pancreatic cancer or not, using the measured expression level and a control expression level similarly measured in a healthy subject.

12. The method of claim 11 , wherein the subject is a human.

13. The method of claim 11 or 12, wherein the sample is blood, serum, or plasma.

14. Use of miR-4736 polynucleotide as a pancreatic cancer marker for detecting pancreatic cancer.

15. miR-6893-5p、miR-6075、miR-6820-5p、miR-4294、miR-6729-5p、miR-4476 、miR-6765-3p、miR-6799-5p、miR-4530、miR-7641、miR-615-5p 、miR-8073、miR-663a、miR-4634、miR-4450、miR-4792、miR-665、miR-7975 、miR-7109-5p、miR-6789-5p、miR-4497、miR-6877-5p、miR- 7977、miR-4734、miR-6821-5p、miR-8089、miR-5585-3p、miR-6085、miR-68 45-5p、miR-4651、miR-433-3p、miR-1231、miR-4665-5p、miR-7114-5p、mi R-1238-5p、miR-8069、miR-4732-5p、miR-619-5p、miR-3622a-5p、miR-126 0a、miR-6741-5p、miR-6781-5p、miR-6125、miR-6805-5p、miR-6132、miR-6 872-3p、miR-6875-5p、miR-1908-3p、miR-4433b-3p、miR-5100、miR-6724- 5p、miR-7107-5p、miR-6726-5p、miR-3185、miR-4638-5p、miR-1273g-3p、m iR-6778-5p、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-1913、miR-465 6、miR-1260b、miR-7106-5p、miR-6889-5p、miR-6780b-5p、miR-6090、miR- 4534、miR-449、miR-5195-3p、miR-1202、miR-4467、miR-6515-3p、miR-42 81、miR-4505、miR-4484、miR-6805-3p、miR-3135b、miR-3162-5p、miR-676 8-5p、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-6757-5p, miR-3131, miR-1343-3p, miR-6775-5p, miR-6813-5p and miR-3940-5p, and / or m iR-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, m iR-451a, miR-24-3p, miR-187-5p, miR-1908-5p, miR-371a-5p, miR-550a-5p, 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-128-1-5 p, 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-6 The use according to claim 14, further comprising one or more polynucleotides selected from the group consisting of miR-665 and miR-8072, miR-806-5p, miR-6842-5p, miR-6716-5p, miR-557, miR-4673, miR-4674, miR-4442, miR-1915-3p, miR-4687-3p, and miR-92b-3p (excluding a combination of polynucleotides comprising miR-665 and miR-8072 and a combination of polynucleotides comprising miR-4665-5p and miR-1469).

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