Abstract: Provided are a liver cancer detection kit or device and a detection method. The present invention pertains to a liver cancer detection kit or device that includes a nucleic acid capable of specifically binding to miRNA in an analyte of a specimen and to a method for detecting liver cancer that includes a step for measuring the miRNA in vitro.
The invention relates to the detection of liver cancer, said miRNA expression amount measuring Kit for detection of liver cancer, including specific miRNA in the subjects used to test for the presence or absence of disease to liver cancer, and that can be merged into specific nucleic acid or devices, and the nucleic acids including.
His innovations.
[0002]
Liver is the largest internal organ in the body is in the upper right abdomen, its main role in detoxification metabolism of nutrients and hazardous substances and emissions. National Research Development Corporation National Cancer Research Center for cancer of cancer in Japan in 2011 to disclose information center statistics, liver cancer, according to cancer to liver cancer patients number who 47271, that 35 people of Japanese one, and is affected by the number of no. 6 cancer site. Likely than women to suffer from men are nearly twice as high. Number of deaths from liver cancer climb 30690 people fit men and women, but the number of deaths # 4 cancer is. Also, in the United States estimated liver cancer in 2014, the incidence of fatality about 23000 people, 33190 people (non-patent literature 1).
[0003]
Often refers to the liver cell cancer accounts for approximately 8% of metastatic liver cancer in General, but on the other all metastatic liver cancer 1-2% of liver in bile duct cancer, bile duct cyst cyst gland planes any more rare cancer species.
[0004]
Determined by a liver cancer progression is divided into hepatocellular carcinoma and liver in bile duct cancer in non-patent literature 2. Here especially liver cancer's spread of the tumor (T0-4) the lymph nodes by the degree of metastasis (N0, N1), distant metastases (M0, M1), classified in stage I (T1/N0/M0), stage II (T2/N0/M0), stage IIIA (T3a/N0/M0), stage IIIB (T3b/N0/M0), and stage IIIC (T4/N0/M0) and stage IVA (N1/M0) and stage IVB (M1).
[0005]
Liver cancer five-year relative survival rate depends on progress. In the case in, according to the non-patent literature 1 and confined to liver cancer (stage 1, stage 2 and stage 3 part) is 28%, near the liver metastasis unless permitted by (stage IVA and stage IIIC) 7% were metastatic (stage IVB) reported 2 percent. Therefore, treatment, discovered in the early stages of liver cancer metastasis and contribution to improve the survival rate.
[0006]
Liver cancer treatment is dominated by three local therapy kills cancer you can cauterize or injecting the drug and surgical treatment and needle hepatectomy and liver transplantation and hepatic artery embolization and, these combined drug therapy and radiation therapy. Especially do not allow cancer to blood vessels and surrounding areas in the early stage of liver cancer to cure in a partial resection of the liver most (non-patent literature 1). On the other hand, if the resection is impossible due to tumour found in localized tumors were large, adjacent to blood vessels, liver transplant, found the transition to be done systemic drug therapy or radiation therapy (non-patent literature 1).
[0007]
As described in the non-patent literature 1, preliminary tests of the liver cancer, she, in addition to palpation, ultrasonography, computed tomography, magnetic resonance imaging, imaging procedures such as angiography is. In addition, liver cancer is known as a tumor marker for detection of AFP (alpha fetoprotein) and Pivka-II (PBC,-to-) and tend to be carried out in conjunction with ultrasound. Perform a biopsy if the findings in these primary liver cancer is suspected, poke the needle through the lesion as a secondary test, cells and tissues collected and examined under a microscope.
[0008]
On the other hand, have made thedeveloped hepatitis liver cancer is suspected because they know the most important liver cancer occurs mainly by long-term infection of B and C type hepatitis virus in addition to the above primary inspection.
[0009]
In the research phase, patent literature 1-how to detect liver cancer using mRNA in a biological sample, as shown in 5 to blood and liver tissue micro RNA (miRNA), have been reported.
[0010]
How to detect breast cancer and liver cancer, leukemia, used as a marker in miRNA in the patent literature 1 hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-92a-2-5p and hsa-miR-92b-5p are shown.
[0011]
How to diagnose various cancers using marker as containing vesicle fluid circulate in the patent literature 2 hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-24-3p, hsa-miR-557, hsa-miR-564, hsa-miR-614, hsa-miR-150-3p, hsa-miR-486-3p, miRNA is reported.
[0012]
Has been shown to detect various diseases including liver cancer, using as a marker of tissue or body fluid hsa-miR-23b-3p, hsa-miR-30c-1-3p, hsa-miR-125a-3p, hsa-miR-486-3p, miRNA in patent literature 3.
[0013]
Circulate fluid in the patent literature 4 vesicles containing hsa-miR-16-5p, hsa-miR-92a-3p, and hsa-miR-has been shown to detect various diseases including liver cancer, 663 a, used as a marker protein, miRNA, hsa-miR-1913, hsa-miR-625-3p.
[0014]
Have shown that plasma HSY-Mir-187-5p, HSY-Mir-92y-3p, HSY-Mir-16-5p, HSY-Mir-30C-1-3p markers for colorectal cancer, liver cancer, lung cancer in the patent literature 5.
Prior art documents
Patent documents
[0015]
Patent literature 1: international publication No. 2010 / 123043 No.
Patent literature 2: United States patent application publication No. 2011 / 003704,
Patent literature 3: international publication No. 2010 / 054386,
Patent literature 4: international publication No. 2012 / 174282 No.
Patent literature 5: international public no. 2011 / 076142 No.
Non-patent literature
[0016]
Non-patent literature 1: American Cancer Society "Liver Cancer", in 2013, p. 5-8, 14-15, 17-23, 27-41
Non-patent literature 2: Sobin, l. The TNM Classification of Malignant Tumours, 7th Edition 2010, p. 104-107
Non-patent literature 3: HCCN guidelines "Hepatobiliary Cancer, 2nd Edition", in 2014, MS-4
Non-patent literature 4: Zhang, B and Yang, B. And in 1999, the Journal of Medical Screening, volume no. 6 (2), p. 108-110
Non-patent literature 5: Takahashi, A... By 2008, the World Journal of Gastroenterology, vol. 14 (1), p. 129-31
Summary of the invention
Inventors are trying to solve a problem
[0017]
Challenges of the present invention is a novel liver cancer to provide how to detect liver cancer effectively using the heading marker, said marker specifically binding DNA.
[0018]
In cancer liver cancer symptoms and it said no as it progresses the cancer, early detection is difficult. Also, most of the liver is stored in the right rib cage, is detected by palpation is hard for. Currently, the hepatitis virus infection and cirrhosis of the liver and liver cancer for the general population there are no risks, screening for liver cancer available is not established (non-patent literature 1). Ultrasound less burden on the patient and also liver cancer is widely used because it is easy to test way, but depending on the location of the cancer detection is difficult and, also, that should be used in conjunction with the tumor marker test results are highly dependent on the skilled laboratory technicians for the (non-patent literature 3). Liver cancer is found is known as a tumor marker for detection of AFP AFP increase ongoing and liver cancer, which had spread to non-resection or hepatic is often non-patent literature 1. In addition, meanwhile reported some liver cancers that do not produce the AFP AFP rises in liver cancer non-cancer, e.g. testicular cancer, ovarian cancer or, to rise further in the cancer liver disease, for instance persistent hepatitis virus infection, including because it is known that specificity is low markers and (non-patent literature 1). For example, to coerce economic and physical burden on patients by applying wrong and discontinuing treatment appropriate to diagnose liver cancer and other cancers, and health care; Test performance is missing, according to the results of the large screening studies using persistent hepatitis patients infected with hepatitis B and (non-patent literature 4) without liver cancer by AFP detection sensitivity is only 69 percent, to use as a screening test for liver cancer. Also, for CT and MRI to detect liver cancer, high-performance is possible, although special equipment is required, and the inspection fee is expensive, as preliminary tests widely used is inappropriate in.
[0019]
Reports also determine liver cancer using mRNA is in the research stage blood and other biological samples in micro RNA (miRNA) that have shown below, but none yet practical.
[0020]
In the patent literature 1 blood cells and have shown how to detect breast cancer and liver cancer, leukemia, used as a marker in miRNA in hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-92a-2-5p and hsa-miR-92b-5p. However, this detection method sample available for tissue ablation surgery is required and a heavy physical burdens of patients with this stage testing approach is not desirable. Also mentioned on the patent literature 1, this detection method, to determine liver cancer specific accuracy, sensitivity, specificity, accuracy, poor industrial utility.
[0021]
How to diagnose various cancers using marker as containing vesicle fluid circulate in the patent literature 2 hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-24-3p, hsa-miR-557, hsa-miR-564, hsa-miR-614, hsa-miR-150-3p, hsa-miR-486-3p, miRNA is reported. A description of how to diagnose a specific liver cancer however using this method in the patent literature 2, also no mention about the accuracy to detect liver cancer, sensitivity, specificity, detection performance for the industrial development of scarce.
[0022]
Has been shown to detect various diseases including liver cancer, using as a marker of tissue or body fluid hsa-miR-23b-3p, hsa-miR-30c-1-3p, hsa-miR-125a-3p, hsa-miR-486-3p, miRNA in patent literature 3. However, this detection method has the original mouse model of experimental results, for the detection of liver cancer in humans is unclear. Also for no description to determine liver cancer to the patent literature 3, precision, sensitivity, specificity, detection performance for the industrial development of scarce.
[0023]
Circulate fluid in the patent literature 4 vesicles containing hsa-miR-16-5p, hsa-miR-92a-3p, and hsa-miR-has been shown to detect various diseases including liver cancer, 663 a, used as a marker protein, miRNA, hsa-miR-1913, hsa-miR-625-3p. Describes how to diagnose a specific liver cancer however in the patent literature 4, using this method, and lack of reliability for above miRNA markers are not validated in an independent sample group.
[0024]
Have shown that plasma hsa-miR-187-5p, hsa-miR-92a-3p, hsa-miR-16-5p, hsa-miR-30c-1-3p, markers for colorectal cancer, liver cancer, lung cancer in the patent literature 5. However, these markers is not a marker to determine from a group consisting of liver cancer, lung cancer, and Ken yomimasu of colon cancer, to detect liver cancer marker.
[0025]
To use these or like this, detection of liver cancer, tumor marker for existing performance low, also on the marker of how performance and detection specifically does not contain a Ken yomimasu liver cancer useless additional inspection due to false positives with patients, liver cancer is the possibility of lost treatment opportunity by overlooking the patient. In addition, several dozen-difficult to use large scale screening for increased inspection costs measure the miRNA consisting of several hundred pieces of health such as. Also, collecting liver tissue to measure tumor markers to give patients less invasive and undesirable for the low allows detection of blood samples can be invasive, liver cancer patients with liver cancer liver cancer patients and Ken yomimasu Ken yomimasu and correctly identify the precise marker is required. High-sensitivity can be detected, especially liver cancer is found early, treatment can improve the survival rate, is also in low-stage liver cancer may be cured by partial resection of the liver, liver cancer marker is demanded.
Means for resolving problems
[0026]
To resolve the above issues inventors as a result of the study low reached the finding that liver cancer can be detected significantly by using nucleic acid can be merged specifically to this heading genes that can be used to detect liver cancer several blood samples can be invasive, to perfect the invention.
[0027]
Summary of the invention
Namely, the invention has the following features.
0030]
(3) wherein nucleic acid is below (a)-(e) the polynucleotide indicates:
(a) 1-167 and 714-nucleotide sequence represented in either 729 polynucleotide composed of u t in the nucleotide sequence or array, the mutants, derivatives, or 15 or more consecutive bases, including their fragments,
(b) 1-167 and 714-polynucleotide containing a nucleotide sequence is represented in either 729
(c) 1-167 and 714-nucleotide sequence represented in either 729 array or u t in the nucleotide sequences phase polynucleotide comprising a nucleotide sequence complementary, the mutants, derivatives, or 15 or more consecutive bases, including their fragments,
(d) 1-167 and 714-bases represented in either 729 or u t in the nucleotide array sequences phase polynucleotide containing a nucleotide complementary and
(e) subparagraph (a) to (d) or polynucleotides and polynucleotide hybridized under stringent conditions,
From a polynucleotide selected from the group in the to (1) or (2) of Kit.
[0031]
(4) wherein Kit is another liver cancer marker that, miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187-5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, least one selected from the group consisting of miR-92a-3p and miR-663 a polynucleotide and nucleic acids that can be merged specifically to further, including (1)-(3) either in Kit.
[0032]
(5) miR-23b-3p is hsa-miR-23b-3p and miR-23a-3p is hsa-miR-23a-3p and miR-625-3p is a hsa-miR-625-3p, miR-1228-3p is hsa-miR-1228-3p, miR-614 is a hsa-miR-614, miR-1913 is a hsa-miR-1913, miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-187-5p is hsa-miR-187-5p and miR-16-5p is hsa-miR-16-5p and miR-92b-3p is a hsa-miR-92b-3p, miR-150-3p is hsa-miR-150-3p, miR-564 is a hsa-miR-564, miR-125a-3p is a hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, and miR-92a-3p is a hsa-miR-92a-3p and miR-663 a in hsa-miR-663 a (4) in the kit mentioned.
[0033]
(6) said nucleic acid is below (f) to (j) to polynucleotides that:
(f) an array number 168-base is represented by one of the 183 that piece of polynucleotide arrays or from u t in the nucleotide sequences, the mutants, derivatives, or 15 or more consecutive bases, including the
(g) an array number 168-polynucleotide containing a nucleotide sequence that is represented by one of the 183
(h) an array number 168-base is represented by one of the 183 array or u t in the nucleotide sequences phase polynucleotide comprising a nucleotide sequence complementary, the mutants, derivatives, or 15 or more consecutive bases, including their fragments,
(i) an array number 168-base is represented by one of the 183 array or u t in the nucleotide sequences phase polynucleotide containing a nucleotide complementary and
(j) above (f) to (I) either polynucleotides and polynucleotide hybridized under stringent conditions,
From a polynucleotide selected from the group in the to (4) or (5) of Kit.
[0034]
(7) wherein Kit is another liver cancer marker that, miR-4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180, miR-6087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466 , miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, polynucleotide selected from the group consisting of miR-557 and miR-6090 at least one more and that can be merged into specific nucleic acids in addition, including (1)-(6) either in Kit
0040]
(13) wherein nucleic acid is below (a)-(e) the polynucleotide indicates:
(a) 1-167 and 714-nucleotide sequence represented in either 729 polynucleotide composed of u t in the nucleotide sequence or array, the mutants, derivatives, or 15 or more consecutive bases, including their fragments,
(b) 1-167 and 714-polynucleotide containing a nucleotide sequence is represented in either 729
(c) 1-167 and 714-nucleotide sequence represented in either 729 array or u t in the nucleotide sequences phase polynucleotide comprising a nucleotide sequence complementary, the mutants, derivatives, or 15 or more consecutive bases, including their fragments,
(d) 1-167 and 714-bases represented in either 729 or u t in the nucleotide array sequences phase polynucleotide containing a nucleotide complementary and
(e) subparagraph (a) to (d) or polynucleotides and polynucleotide hybridized under stringent conditions,
From a polynucleotide selected from the group in the (11) or (12) device.
[0041]
(14) wherein devices of different liver cancer marker that, miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187-5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, nucleic acid that can be merged in the singular and at least one or more selected from the group consisting of miR-92a-3p and miR-663 a polynucleotide including addition, (11) and (13) to one device.
[0042]
(15) miR-23b-3p is hsa-miR-23b-3p and miR-23a-3p is hsa-miR-23a-3p and miR-625-3p is a hsa-miR-625-3p, miR-1228-3p is hsa-miR-1228-3p, miR-614 is a hsa-miR-614, miR-1913 is a hsa-miR-1913, miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-187-5p is hsa-miR-187-5p and miR-16-5p is hsa-miR-16-5p and miR-92b-3p is a hsa-miR-92b-3p, miR-150-3p is hsa-miR-150-3p, miR-564 is a hsa-miR-564, miR-125a-3p is a hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, and Mir-92y-3p is a HSY-Mir-92y-3p and miR-663 a is 663 a HSY-Mir-, (14) to the device.
[0043]
(16) said nucleic acid is below (f) to (j) to polynucleotides that:
(f) an array number 168-base is represented by one of the 183 that piece of polynucleotide arrays or from u t in the nucleotide sequences, the mutants, derivatives, or 15 or more consecutive bases, including the
(g) an array number 168-polynucleotide containing a nucleotide sequence that is represented by one of the 183
(h) an array number 168-base is represented by one of the 183 array or u t in the nucleotide sequences phase polynucleotide comprising a nucleotide sequence complementary, the mutants, derivatives, or 15 or more consecutive bases, including their fragments,
(i) an array number 168-base is represented by one of the 183 array or u t in the nucleotide sequences phase polynucleotide containing a nucleotide complementary and
(j) above (f) to (I) either polynucleotides and polynucleotide hybridized under stringent conditions,
From a polynucleotide selected from the group in, (14) or (15) device.
[0044]
(17) wherein devices of different liver cancer marker that, miR-4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180, miR-6087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, nucleic acid that can be merged in the singular and polynucleotides for at least one or more selected from the group consisting of miR-6778-5p, miR-557 and miR-6090 including further, (11) and (16) into one device.
The scope of the claims
[Claim 1]
A liver cancer marker, miR-1343-3p, miR-6726-5p, miR-6515-3p, miR-4651, miR-4257, miR-3188, miR-6131, miR-6766-3p, miR-7641 , miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977, miR-7110-5p , miR-6717-5p, miR-6870-5p, miR-663b, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706 , miR-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6857-5p, miR-1227-5p, miR-6741-5p, miR-451a, miR-8063, miR-3622a-5p , miR-615-5p, miR-128-1-5p, miR-6825-5p, miR-1260b, miR-4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR -6840-3p, miR-6765-5p, miR-296-5p, miR-3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6784-5p, miR-6749 -5p, miR-1231, miR-4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791 -5p, miR-3185, miR-1260a, miR-3197, miR-6845-5p, miR-6887-5p, miR-6738-5p, miR-6872-3p, miR-4497, miR-1229-5p, miR -6820-5p, miR-6777-5p, miR-3917, miR-5787, miR-4286, miR-6877-5p, miR-1225-3p, miR-6088, miR-6800-5p, miR-1246, miR -4467, miR-4419b, miR-1914-3p, miR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p , miR-1228-5p, miR-5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR -6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891-5p, miR-6826-5p, miR-6807-5p, miR-7150, miR -4534, miR-4476, miR-4649-5p, miR-4525, miR-1915-3p, miR-4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848-5p , miR-4739, miR-4459, miR-1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR-6510-5p, miR-1343-5p, miR -1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858-5p, miR-3937, miR-939-5p, miR-3656, miR-744-5p, miR -4687-3p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p , miR-5195-3p, miR-1185-1-3p, miR-6774-5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR-4508 , miR-6806-5p, miR-7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752-5p, miR-6724-5p, miR-6757 -5p, miR-4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR-4484, miR-4634, miR-4745-5p, miR-4730 , miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p and at least one polynucleotide capable of specifically binding a nucleic acid selected from the group consisting of miR-6836-3p the including, kit for detecting liver cancer.
[Claim 2]
miR-1343-3p is hsa-miR-1343-3p, miR- 6726-5p is hsa-miR-6726-5p, miR- 6515-3p is hsa-miR-6515-3p, miR- 4651 is hsa-miR-4651, miR- 4257 is hsa-miR-4257, miR- 3188 is hsa-miR-3188, miR- 6131 is hsa-miR-6131, miR- 6766- 3p is hsa-miR-6766-3p, miR- 7641 is hsa-miR-7641, miR- 1249 is hsa-miR-1249, miR- 3679-3p is in hsa-miR-3679-3p Yes, miR-6787-5p is hsa-miR-6787-5p, miR- 4454 is hsa-miR-4454, miR- 3135b is hsa-miR-3135b, the miR-6765-3p hsa- is a miR-6765-3p, miR-7975 is hsa-miR-7975, miR- 204-3p is hsa-miR-204-3p, miR- 7977 is hsa-miR-7977, miR- 7110-5p is hsa-miR-7110-5p, miR- 6717-5p is hsa-miR-6717-5p, miR- 6870-5p is hsa-miR-6870-5p, the miR-663b It is hsa-miR-663b, miR- 6875-5p is hsa-miR-6875-5p, miR- 8072 is hsa-miR-8072, miR- 6816-5p is in hsa-miR-6816-5p Yes, miR-4281 is hsa-miR-4281, miR- 6729-5p is hsa-miR-6729-5p, miR- 8069 is hsa-miR-8069, miR- 4706 is hsa-miR- is 4706, miR-7108-5p is hsa-miR-7108-5p, miR- 4433b-3p is hsa-miR-4433b-3p, miR-6893-5p is in hsa-miR-6893-5p Yes, miR-6857-5p is hsa-miR-6857-5p, miR- 1227-5p is hsa-miR-1227-5p, miR- 6741-5p is hsa-miR-6741-5p, miR-451a is hsa-miR-451a, miR- 8063 is hsa-miR-8063, miR- 3622a-5p is hsa-miR-3622a-5p, miR-615-5p is hsa-miR- a 615-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR- 6825-5p is hsa-miR-6825-5p, miR- 1260b is hsa-miR- is 1260b, miR-4433-3p is hsa-miR-4433-3p, miR- 4665-5p is hsa-miR-4665-5p, miR- 7845-5p is in hsa-miR-7845-5p Yes, miR-1908-5p is hsa-miR-1908-5p, miR- 6840-3p is hsa-miR-6840-3p, miR- 6765-5p is hsa-miR-6765-5p, miR-296-5p is hsa-miR-296-5p, miR- 3675-3p is hsa-miR-3675-3p, miR- 6781-5p is hsa-miR-6781-5p, miR- 423-5p is hsa-miR-423-5p, miR- 3663-3p is hsa-miR-3663-3p, miR- 6784-5p is hsa-miR-6784-5p, miR- 6749- 5p is hsa-miR-6749-5p, miR- 1231 is hsa-miR-1231, miR- 4746-3p is hsa-miR-4746-3p, miR- 6780b-5p is hsa-miR- a 6780b-5p, miR-4758-5p is hsa-miR-4758-5p, miR- 3679-5p is hsa-miR-3679-5p, miR- 3184-5p is hsa-miR-3184- a 5p, miR-6125 is hsa-miR-6125, miR- 6721-5p is hsa-miR-6721-5p, miR- 6791-5p is hsa-miR-6791-5p, miR- 3185 is hsa-miR-3185, miR- 1260a is hsa-miR-1260a, miR- 3197 is hsa-miR-3197, miR- 6845-5p is hsa-miR-6845-5p, miR-6887-5p is hsa-miR-6887-5p, miR- 6738-5p is hsa-miR-6738-5p, miR- 6872-3p is hsa-miR-6872-3p, miR- 4497 is hsa-miR-4497, miR- 1229-5p is hsa-miR-1229-5p, miR- 6820-5p is hsa-miR-6820-5p, the miR-6777-5p hsa- is a miR-6777-5p, miR-3917 is hsa-miR-3917, miR- 5787 is hsa-miR-5787, miR- 4286 is hsa-miR-4286, is miR-6877-5p is hsa-miR-6877-5p, miR- 1225-3p is hsa-miR-1225-3p, miR- 6088 is hsa-miR-6088, miR- 6800-5p is hsa-miR-6800- a 5p, miR-1246 is hsa-miR-1246, miR- 4467 is hsa-miR-4467, miR- 4419b is hsa-miR-4419b, miR- 1914-3p is hsa-miR- a 1914-3p, miR-4632-5p is hsa-miR-4632-5p, miR- 1915-5p is hsa-miR-1915-5p, miR- 3940-5p is hsa-miR-3940- a 5p, miR-1185-2-3p is hsa-miR-1185-2-3p, miR- 6746-5p is hsa-miR-6746-5p, miR- 5001-5p is hsa-miR- a 5001-5p, miR-1228-5p is hsa-miR-1228-5p, miR- 5572 is hsa-miR-5572, miR- 4327 is hsa-miR-4327, miR- 4638- 5p is hsa-miR-4638-5p, miR- 6799-5p is hsa-miR-6799-5p, miR- 6861-5p is hsa-miR-6861-5p, the miR-6727-5p is hsa-miR-6727-5p, miR- 4513 is hsa-miR-4513, miR- 6805-3p is hsa-miR-6805-3p, miR- 6808-5p is hsa-miR-6808- a 5p, miR-4449 is hsa-miR-4449, miR- 1199-5p is hsa-miR-1199-5p, miR- 1275 is hsa-miR-1275, miR- 4792 is hsa- is a miR-4792, miR-4443 is hsa-miR-4443, miR- 6891-5p is hsa-miR-6891-5p, miR- 6826-5p is hsa-miR-6826-5p, miR-6807-5p is hsa-miR-6807-5p, miR- 7150 is hsa-miR-7150, miR- 4534 is hsa-miR-4534, miR- 4476 is in the hsa-miR-4476 Yes, miR-4649-5p is hsa-miR-4649-5p, miR- 4525 is hsa-miR-4525, miR- 1915-3p is hsa-miR-1915-3p, the miR-4516 is hsa-miR-4516, miR- 4417 is hsa-miR-4417, miR- 642b-3p is hsa-miR-642b-3p, miR-3141 is hsa-miR-3141, miR- 5100 is hsa-miR-5100, miR- 6848-5p is hsa-miR-6848-5p, miR- 4739 is hsa-miR-4739, miR- 4459 is hsa-miR-4459, miR-1237-5p is hsa-miR-1237-5p, miR- 296-3p is hsa-miR-296-3p, miR- 4665-3p is hsa-miR-4665-3p, miR- 6786-5p is hsa-miR-6786-5p, miR- 4258 is hsa-miR-4258, miR- 6510-5p is hsa-miR-6510-5p, the miR-1343-5p hsa- is a miR-1343-5p, miR-1247-3p is hsa-miR-1247-3p, miR- 6805-5p is hsa-miR-6805-5p, miR- 4492 is in the hsa-miR-4492 Yes, miR-1469 is hsa-miR-1469, miR- 1268b is hsa-miR-1268b, miR- 6858-5p is hsa-miR-6858-5p, miR- 3937 is hsa-miR- is 3937, miR-939-5p is hsa-miR-939-5p, miR- 3656 is hsa-miR-3656, miR- 744-5p is hsa-miR-744-5p, miR- 4687-3p is hsa-miR-4687-3p, miR- 4763-3p is hsa-miR-4763-3p, miR- 3620-5p is hsa-miR-3620-5p, the miR-3195 is hsa-miR-3195, miR- 6842-5p is hsa-miR-6842-5p, miR- 4707-5p is hsa-miR-4707-5p, miR- 642a-3p is hsa-miR- a 642a-3p, miR-7113-3p is hsa-miR-7113-3p, miR- 4728-5p is hsa-miR-4728-5p, miR- 5195-3p is hsa-miR-5195- is 3p, miR-1185-1-3p is hsa-miR-1185-1-3p, miR- 6774-5p is hsa-miR-6774-5p, miR- 8059 is in the hsa-miR-8059 Yes, miR-3131 is hsa-miR-3131, miR- 7847-3p is hsa-miR-7847-3p, miR- 4463 is hsa-miR-4463, is miR-128-2-5p is hsa-miR-128-2-5p, miR- 4508 is hsa-miR-4508, miR- 6806-5p is hsa-miR-6806-5p, miR- 7111-5p is hsa-miR- a 7111-5p, miR-6782-5p is hsa-miR-6782-5p, miR- 4734 is hsa-miR-4734, miR- 3162-5p is hsa-miR-3162-5p, miR-887-3p is hsa-miR-887-3p, miR- 6752-5p is hsa-miR-6752-5p, miR- 6724-5p is hsa-miR-6724-5p, miR- 6757-5p is hsa-miR-6757-5p, miR- 4448 is hsa-miR-4448, miR- 671-5p is hsa-miR-671-5p, miR- 3178 is hsa-miR- is 3178, miR-4725-3p is hsa-miR-4725-3p, miR- 940 is hsa-miR-940, miR- 6789-5p is hsa-miR-6789-5p, miR- 4484 is hsa-miR-4484, miR- 4634 is hsa-miR-4634, miR- 4745-5p is hsa-miR-4745-5p, miR- 4730 is
hsa-mi be the R-4730 , miR-6803-5p is hsa-miR-6803-5p, miR- 6798-5p is hsa-miR-6798-5p, miR- 3648 is hsa-miR-3648, miR- 4783-3p there is a hsa-miR-4783-3p, and, miR-6836-3p is hsa-miR-6836-3p, kit according to claim 1.
[Claim 3]
Said nucleic acid, the following (a) ~ (e) to indicate a
polynucleotide: (a) a base u in the nucleotide sequence or the nucleotide sequence shown in any of SEQ ID NOs 167 and 714-729 is t a polynucleotide consisting of the sequence, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (b) SEQ ID NOs 167 and 714-729 ,
polynucleotides, variants thereof u in the nucleotide sequence or the nucleotide sequence represented by any one of (c)
complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (d) SEQ ID NOs 167 and 714-729 polynucleotides comprising a nucleotide sequence, and
(e) above (a) ~ any polynucleotide under stringent conditions with a polynucleotide hybridizing of (d-),
a polynucleotide selected from the group consisting of, the kit according to claim 1 or 2.
[Claim 4]
The kit is another of liver cancer markers, miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2 -5p, miR-187-5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3p and miR -663a further comprising at least one polynucleotide capable of specifically binding nucleic acid is selected from the group consisting of, kit according to any one of claims 1 to 3.
[Claim 5]
miR-23b-3p is hsa-miR-23b-3p, miR-23a-3p is hsa-miR-23a-3p, miR-625-3p is hsa-miR-625-3p, miR- 1228-3p is hsa-miR-1228-3p, miR-614 is hsa-miR-614, miR-1913 is hsa-miR-1913, miR-92a-2-5p is hsa-miR- a 92a-2-5p, miR-187-5p is hsa-miR-187-5p, miR-16-5p is hsa-miR-16-5p, miR-92b-3p is hsa-miR- is a 92b-3p, miR-150-3p is hsa-miR-150-3p, miR-564 is hsa-miR-564, miR-125a-3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-92a-3p is hsa-miR-92a-3p, and, miR-663a is hsa-miR-663a, to claim 4 the kit according.
[6.]
It said nucleic acid, the following (f) ~ (j) are shown polynucleotide:
(f) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 168-183 are the nucleotide sequence is t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 168 to
183, (h) SEQ ID NO: 168 to polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 183 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
(i) SEQ ID NO: 168 to a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 183, and
(j) wherein (f) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (i),
a polynucleotide selected from the group consisting of a kit according to claim 4 or 5.
[7.]
The kit is another of liver cancer markers, miR-4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180 , miR-6087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486 -3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR -371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR -6089, miR-6124, miR-6778-5p, further comprising at least one polynucleotide capable of specifically bound nucleic acid is selected from the group consisting of miR-557 and miR-6090, claim 1 6 kit according to any one of.
[8.]
miR-4688 is hsa-miR-4688, miR-4648 is hsa-miR-4648, miR-6085 is hsa-miR-6085, miR-6126 is hsa-miR-6126, miR- 6880-5p is hsa-miR-6880-5p, miR-328-5p is hsa-miR-328-5p, miR-6768-5p is hsa-miR-6768-5p, the miR-3180 is hsa-miR-3180, miR-6087 is hsa-miR-6087, miR-1273g-3p is hsa-miR-1273g-3p, miR-1225-5p is in hsa-miR-1225-5p Yes, miR-3196 is hsa-miR-3196, miR-4695-5p is hsa-miR-4695-5p, miR-6732-5p is hsa-miR-6732-5p, miR-638 is is hsa-miR-638, miR-6813-5p is hsa-miR-6813-5p, miR-665 is hsa-miR-665, miR-486-3p is in hsa-miR-486-3p Yes, miR-4466 is hsa-miR-4466, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-3621 is hsa-miR-3621, miR-6743- 5p is hsa-miR-6743-5p, miR-4298 is hsa-miR-4298, miR-4741 is hsa-miR-4741, miR-3619-3p is in hsa-miR-3619-3p Yes, miR-6824-5p is hsa-miR-6824-5p, miR-5698 is hsa-miR-5698, miR-371a-5p is hsa-miR-371a-5p, the miR-4488 is hsa-miR-4488, miR-1233-5p is hsa-miR-1233-5p, miR-4723-5p is hsa-miR-4723-5p, miR-24-3p is hsa-miR- a 24-3p, miR-1238-5p is hsa-miR-1238-5p, miR-4442 is hsa-miR-4442, miR-3928-3p is hsa-miR-3928-3p, miR-6716-5p is hsa-miR-6716-5p, miR-6089 is hsa-miR-6089, miR-6124 is hsa-miR-6124, miR-6778-5p is hsa-miR- a 6778-5p, miR-557 is hsa-miR-557, and, miR-6090 is hsa-miR-6090, kit according to claim 7.
[9.]
It said nucleic acid, the following (k) a polynucleotide shown in ~ (o):
(k) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 184-224 are the nucleotide sequence is t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 184 -
224, (yd) SEQ ID NO: 184 ~ polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 224 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 184-224, and
(o) the (k) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (n),
is a polynucleotide selected from the group consisting of a kit according to claim 7 or 8.
[10.]
The kit includes all of the at least two or more nucleic acids respectively capable of specifically binding at least two or more polynucleotides from liver cancer marker selected according to claim 1 or 2, Claim 1 the kit according to any one of 1-9.
[11.]
A liver cancer marker, miR-1343-3p, miR-6726-5p, miR-6515-3p, miR-4651, miR-4257, miR-3188, miR-6131, miR-6766-3p, miR-7641 , miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977, miR-7110-5p , miR-6717-5p, miR-6870-5p, miR-663b, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706 , miR-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6857-5p, miR-1227-5p, miR-6741-5p, miR-451a, miR-8063, miR-3622a-5p , miR-615-5p, miR-128-1-5p, miR-6825-5p, miR-1260b, miR-4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR -6840-3p, miR-6765-5p, miR-296-5p, miR-3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6784-5p, miR-6749 -5p, miR-1231, miR-4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791 -5p, miR-3185, miR-1260a, miR-3197, miR-6845-5p, miR-6887-5p, miR-6738-5p, miR-6872-3p, miR-4497, miR-1229-5p, miR -6820-5p, miR-6777-5p, miR-3917, miR-5787, miR-4286, miR-6877-5p, miR-1225-3p, miR-6088, miR-6800-5p, miR-1246, miR -4467, miR-4419b, miR-1914-3p, miR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p , miR-1228-5p, miR-5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR -6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891-5p, miR-6826-5p, miR-6807-5p, miR-7150, miR -4534, miR-4476, miR-4649-5p, miR-4525, miR-1915-3p, miR-4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848-5p , miR-4739, miR-4459, miR-1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR-6510-5p, miR-1343-5p, miR -1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858-5p, miR-3937, miR-939-5p, miR-3656, miR-744-5p, miR -4687-3p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p , miR-5195-3p, miR-1185-1-3p, miR-6774-5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR-4508 , miR-6806-5p, miR-7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752-5p, miR-6724-5p, miR-6757 -5p, miR-4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR-4484, miR-4634, miR-4745-5p, miR-4730 , miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p and at least one polynucleotide capable of specifically binding a nucleic acid selected from the group consisting of miR-6836-3p including the, the detection device of liver cancer.
[12.]
miR-1343-3p is hsa-miR-1343-3p, miR- 6726-5p is hsa-miR-6726-5p, miR- 6515-3p is hsa-miR-6515-3p, miR- 4651 is hsa-miR-4651, miR- 4257 is hsa-miR-4257, miR- 3188 is hsa-miR-3188, miR- 6131 is hsa-miR-6131, miR- 6766- 3p is hsa-miR-6766-3p, miR- 7641 is hsa-miR-7641, miR- 1249 is hsa-miR-1249, miR- 3679-3p is in hsa-miR-3679-3p Yes, miR-6787-5p is hsa-miR-6787-5p, miR- 4454 is hsa-miR-4454, miR- 3135b is hsa-miR-3135b, the miR-6765-3p hsa- is a miR-6765-3p, miR-7975 is hsa-miR-7975, miR- 204-3p is hsa-miR-204-3p, miR- 7977 is hsa-miR-7977, miR- 7110-5p is hsa-miR-7110-5p, miR- 6717-5p is hsa-miR-6717-5p, miR- 6870-5p is hsa-miR-6870-5p, the miR-663b It is hsa-miR-663b, miR- 6875-5p is hsa-miR-6875-5p, miR- 8072 is hsa-miR-8072, miR- 6816-5p is in hsa-miR-6816-5p Yes, miR-4281 is hsa-miR-4281, miR- 6729-5p is hsa-miR-6729-5p, miR- 8069 is hsa-miR-8069, miR- 4706 is hsa-miR- is 4706, miR-7108-5p is hsa-miR-7108-5p, miR- 4433b-3p is hsa-miR-4433b-3p, miR-6893-5p is in hsa-miR-6893-5p Yes, miR-6857-5p is hsa-miR-6857-5p, miR- 1227-5p is hsa-miR-1227-5p, miR- 6741-5p is hsa-miR-6741-5p, miR-451a is hsa-miR-451a, miR- 8063 is hsa-miR-8063, miR- 3622a-5p is hsa-miR-3622a-5p, miR-615-5p is hsa-miR- a 615-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR- 6825-5p is hsa-miR-6825-5p, miR- 1260b is hsa-miR- is 1260b, miR-4433-3p is hsa-miR-4433-3p, miR- 4665-5p is hsa-miR-4665-5p, miR- 7845-5p is in hsa-miR-7845-5p Yes, miR-1908-5p is hsa-miR-1908-5p, miR- 6840-3p is hsa-miR-6840-3p, miR- 6765-5p is hsa-miR-6765-5p, miR-296-5p is hsa-miR-296-5p, miR- 3675-3p is hsa-miR-3675-3p, miR- 6781-5p is hsa-miR-6781-5p, miR- 423-5p is hsa-miR-423-5p, miR- 3663-3p is hsa-miR-3663-3p, miR- 6784-5p is hsa-miR-6784-5p, miR- 6749- 5p is hsa-miR-6749-5p, miR- 1231 is hsa-miR-1231, miR- 4746-3p is hsa-miR-4746-3p, miR- 6780b-5p is hsa-miR- a 6780b-5p, miR-4758-5p is hsa-miR-4758-5p, miR- 3679-5p is hsa-miR-3679-5p, miR- 3184-5p is hsa-miR-3184- a 5p, miR-6125 is hsa-miR-6125, miR- 6721-5p is hsa-miR-6721-5p, miR- 6791-5p is hsa-miR-6791-5p, miR- 3185 is hsa-miR-3185, miR- 1260a is hsa-miR-1260a, miR- 3197 is hsa-miR-3197, miR- 6845-5p is hsa-miR-6845-5p, miR-6887-5p is hsa-miR-6887-5p, miR- 6738-5p is hsa-miR-6738-5p, miR- 6872-3p is hsa-miR-6872-3p, miR- 4497 is hsa-miR-4497, miR- 1229-5p is hsa-miR-1229-5p, miR- 6820-5p is hsa-miR-6820-5p, the miR-6777-5p hsa- is a miR-6777-5p, miR-3917 is hsa-miR-3917, miR- 5787 is hsa-miR-5787, miR- 4286 is hsa-miR-4286, is miR-6877-5p is hsa-miR-6877-5p, miR- 1225-3p is hsa-miR-1225-3p, miR- 6088 is hsa-miR-6088, miR- 6800-5p is hsa-miR-6800- a 5p, miR-1246 is hsa-miR-1246, miR- 4467 is hsa-miR-4467, miR- 4419b is hsa-miR-4419b, miR- 1914-3p is hsa-miR- a 1914-3p, miR-4632-5p is hsa-miR-4632-5p, miR- 1915-5p is hsa-miR-1915-5p, miR- 3940-5p is hsa-miR-3940- a 5p, miR-1185-2-3p is hsa-miR-1185-2-3p, miR- 6746-5p is hsa-miR-6746-5p, miR- 5001-5p is hsa-miR- a 5001-5p, miR-1228-5p is hsa-miR-1228-5p, miR- 5572 is hsa-miR-5572, miR- 4327 is hsa-miR-4327, miR- 4638- 5p is hsa-miR-4638-5p, miR- 6799-5p is hsa-miR-6799-5p, miR- 6861-5p is hsa-miR-6861-5p, the miR-6727-5p is hsa-miR-6727-5p, miR- 4513 is hsa-miR-4513, miR- 6805-3p is hsa-miR-6805-3p, miR- 6808-5p is hsa-miR-6808- a 5p, miR-4449 is hsa-miR-4449, miR- 1199-5p is hsa-miR-1199-5p, miR- 1275 is hsa-miR-1275, miR- 4792 is hsa- is a miR-4792, miR-4443 is hsa-miR-4443, miR- 6891-5p is hsa-miR-6891-5p, miR- 6826-5p is hsa-miR-6826-5p, miR-6807-5p is hsa-miR-6807-5p, miR- 7150 is hsa-miR-7150, miR- 4534 is hsa-miR-4534, miR- 4476 is in the hsa-miR-4476 Yes, miR-4649-5p is hsa-miR-4649-5p, miR- 4525 is hsa-miR-4525, miR- 1915-3p is hsa-miR-1915-3p, the miR-4516 is hsa-miR-4516, miR- 4417 is hsa-miR-4417, miR- 642b-3p is hsa-miR-642b-3p, miR-3141 is hsa-miR-3141, miR- 5100 is hsa-miR-5100, miR- 6848-5p is hsa-miR-6848-5p, miR- 4739 is hsa-miR-4739, miR- 4459 is hsa-miR-4459, miR-1237-5p is hsa-miR-1237-5p, miR- 296-3p is hsa-miR-296-3p, miR- 4665-3p is hsa-miR-4665-3p, miR- 6786-5p is hsa-miR-6786-5p, miR- 4258 is hsa-miR-4258, miR- 6510-5p is hsa-miR-6510-5p, the miR-1343-5p hsa- is a miR-1343-5p, miR-1247-3p is hsa-miR-1247-3p, miR- 6805-5p is hsa-miR-6805-5p, miR- 4492 is in the hsa-miR-4492 Yes, miR-1469 is hsa-miR-1469, miR- 1268b is hsa-miR-1268b, miR- 6858-5p is hsa-miR-6858-5p, miR- 3937 is hsa-miR- is 3937, miR-939-5p is hsa-miR-939-5p, miR- 3656 is hsa-miR-3656, miR- 744-5p is hsa-miR-744-5p, miR- 4687-3p is hsa-miR-4687-3p, miR- 4763-3p is hsa-miR-4763-3p, miR- 3620-5p is hsa-miR-3620-5p, the miR-3195 is hsa-miR-3195, miR- 6842-5p is hsa-miR-6842-5p, miR- 4707-5p is hsa-miR-4707-5p, miR- 642a-3p is hsa-miR- a 642a-3p, miR-7113-3p is hsa-miR-7113-3p, miR- 4728-5p is hsa-miR-4728-5p, miR- 5195-3p is hsa-miR-5195- is 3p, miR-1185-1-3p is hsa-miR-1185-1-3p, miR- 6774-5p is hsa-miR-6774-5p, miR- 8059 is in the hsa-miR-8059 Yes, miR-3131 is hsa-miR-3131, miR- 7847-3p is hsa-miR-7847-3p, miR- 4463 is hsa-miR-4463, is miR-128-2-5p is hsa-miR-128-2-5p, miR- 4508 is hsa-miR-4508, miR- 6806-5p is hsa-miR-6806-5p, miR- 7111-5p is hsa-miR- a 7111-5p, miR-6782-5p is hsa-miR-6782-5p, miR- 4734 is hsa-miR-4734, miR- 3162-5p is hsa-miR-3162-5p, miR-887-3p is hsa-miR-887-3p, miR- 6752-5p is hsa-miR-6752-5p, miR- 6724-5p is hsa-miR-6724-5p, miR- 6757-5p is hsa-miR-6757-5p, miR- 4448 is hsa-miR-4448, miR- 671-5p is hsa-miR-671-5p, miR- 3178 is hsa-miR- is 3178, miR-4725-3p is hsa-miR-4725-3p, miR- 940 is hsa-miR-940, miR- 6789-5p is hsa-miR-6789-5p, miR- 4484 is hsa-miR-4484, miR- 4634 is hsa-miR-4634, miR- 4745-5p is hsa-miR-4745-5p, miR- 4730 is
hsa-mi be the R-4730 , miR-6803-5p is hsa-miR-6803-5p, miR- 6798-5p is hsa-miR-6798-5p, miR- 3648 is hsa-miR-3648, miR- 4783-3p there is a hsa-miR-4783-3p, and, miR-6836-3p is hsa-miR-6836-3p, according to claim 11, wherein the device.
[13.]
Said nucleic acid, the following (a) ~ (e) to indicate a
polynucleotide: (a) a base u in the nucleotide sequence or the nucleotide sequence shown in any of SEQ ID NOs 167 and 714-729 is t a polynucleotide consisting of the sequence, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (b) SEQ ID NOs 167 and 714-729 ,
polynucleotides, variants thereof u in the nucleotide sequence or the nucleotide sequence represented by any one of (c)
complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (d) SEQ ID NOs 167 and 714-729 polynucleotides comprising a nucleotide sequence, and
(e) above (a) ~ any polynucleotide under stringent conditions with a polynucleotide hybridizing of (d-),
a polynucleotide selected from the group consisting of, device according to claim 11 or 12.
[14.]
The device is another of liver cancer markers, miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2 -5p, miR-187-5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3p and miR -663a further comprising at least one polynucleotide capable of specifically binding nucleic acid is selected from the group consisting of, a device according to any one of claims 11 to 13.
[15.]
miR-23b-3p is hsa-miR-23b-3p, miR-23a-3p is hsa-miR-23a-3p, miR-625-3p is hsa-miR-625-3p, miR- 1228-3p is hsa-miR-1228-3p, miR-614 is hsa-miR-614, miR-1913 is hsa-miR-1913, miR-92a-2-5p is hsa-miR- a 92a-2-5p, miR-187-5p is hsa-miR-187-5p, miR-16-5p is hsa-miR-16-5p, miR-92b-3p is hsa-miR- is a 92b-3p, miR-150-3p is hsa-miR-150-3p, miR-564 is hsa-miR-564, miR-125a-3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-92a-3p is hsa-miR-92a-3p, and, miR-663a is hsa-miR-663a, to claim 14 device described.
[16.]
It said nucleic acid, the following (f) ~ (j) are shown polynucleotide:
(f) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 168-183 are the nucleotide sequence is t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 168 to
183, (h) SEQ ID NO: 168 to polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 183 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
(i) SEQ ID NO: 168 to a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 183, and
(j) wherein (f) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (i),
a polynucleotide selected from the group consisting of a device according to claim 14 or 15.
[17.]
The device is another of liver cancer markers, miR-4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180 , miR-6087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486 -3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR -371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR -6089, miR-6124, miR-6778-5p, further comprising at least one polynucleotide capable of specifically bound nucleic acid is selected from the group consisting of miR-557 and miR-6090, claims 11 to 16 device according to any one of.
[18.]
miR-4688 is hsa-miR-4688, miR-4648 is hsa-miR-4648, miR-6085 is hsa-miR-6085, miR-6126 is hsa-miR-6126, miR- 6880-5p is hsa-miR-6880-5p, miR-328-5p is hsa-miR-328-5p, miR-6768-5p is hsa-miR-6768-5p, the miR-3180 is hsa-miR-3180, miR-6087 is hsa-miR-6087, miR-1273g-3p is hsa-miR-1273g-3p, miR-1225-5p is in hsa-miR-1225-5p Yes, miR-3196 is hsa-miR-3196, miR-4695-5p is hsa-miR-4695-5p, miR-6732-5p is hsa-miR-6732-5p, miR-638 is is hsa-miR-638, miR-6813-5p is hsa-miR-6813-5p, miR-665 is hsa-miR-665, miR-486-3p is in hsa-miR-486-3p Yes, miR-4466 is hsa-miR-4466, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-3621 is hsa-miR-3621, miR-6743- 5p is hsa-miR-6743-5p, miR-4298 is hsa-miR-4298, miR-4741 is hsa-miR-4741, miR-3619-3p is in hsa-miR-3619-3p Yes, miR-6824-5p is hsa-miR-6824-5p, miR-5698 is hsa-miR-5698, miR-371a-5p is hsa-miR-371a-5p, the miR-4488 is hsa-miR-4488, miR-1233-5p is hsa-miR-1233-5p, miR-4723-5p is hsa-miR-4723-5p, miR-24-3p is hsa-miR- a 24-3p, miR-1238-5p is hsa-miR-1238-5p, miR-4442 is hsa-miR-4442, miR-3928-3p is hsa-miR-3928-3p, miR-6716-5p is hsa-miR-6716-5p, miR-6089 is hsa-miR-6089, miR-6124 is hsa-miR-6124, miR-6778-5p is hsa-miR- a 6778-5p, miR-557 is hsa-miR-557, and, miR-6090 is hsa-miR-6090, according to claim 17, wherein the device.
[19.]
It said nucleic acid, the following (k) a polynucleotide shown in ~ (o):
(k) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 184-224 are the nucleotide sequence is t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 184 -
224, (yd) SEQ ID NO: 184 ~ polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 224 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 184-224, and
(o) the (k) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (n),
is a polynucleotide selected from the group consisting of, a device according to claim 17 or 18.
[20.]
It said device is a device for measuring by hybridization techniques, according to any one of claims 11 to 19 devices.
[21.]
The hybridization techniques, a nucleic acid array technology, according to claim 20 devices.
[22.]
The device includes all of the at least two or more nucleic acids respectively capable of specifically binding at least two or more polynucleotides from liver cancer marker selected according to claim 11 or 12, claim 11 device according to any one of to 21.
[23.]
Using a device according to any one of claims 1 kit according to any one of 10 or claims 11 to 22 to measure the expression level of a target nucleic acid in the specimen of a subject, is the measurement and the expression level was, by using the control expression level in healthy body that is measured in the same manner that the subject is suffering from liver cancer, or be assessed in vitro that liver cancer unaffected including a method for detecting liver cancer.
[24.]
The subject is a human The method of claim 23.
[25.]
The sample is blood, serum or plasma Method according to claim 23 or 24.
| # | Name | Date |
|---|---|---|
| 1 | Sequence listing(PDF) [17-01-2017(online)].pdf | 2017-01-17 |
| 2 | Sequence listing [17-01-2017(online)].txt | 2017-01-17 |
| 4 | PROOF OF RIGHT [17-01-2017(online)].pdf | 2017-01-17 |
| 5 | Power of Attorney [17-01-2017(online)].pdf | 2017-01-17 |
| 6 | Form 5 [17-01-2017(online)].pdf | 2017-01-17 |
| 7 | Form 3 [17-01-2017(online)].pdf | 2017-01-17 |
| 8 | Drawing [17-01-2017(online)].pdf | 2017-01-17 |
| 9 | Description(Complete) [17-01-2017(online)].pdf_7.pdf | 2017-01-17 |
| 10 | Description(Complete) [17-01-2017(online)].pdf | 2017-01-17 |
| 11 | Other Document [24-02-2017(online)].pdf | 2017-02-24 |
| 12 | Marked Copy [24-02-2017(online)].pdf | 2017-02-24 |
| 13 | Form 13 [24-02-2017(online)].pdf | 2017-02-24 |
| 14 | Description(Complete) [24-02-2017(online)].pdf_444.pdf | 2017-02-24 |
| 15 | Description(Complete) [24-02-2017(online)].pdf | 2017-02-24 |
| 16 | Information under section 8(2) [29-06-2017(online)].pdf | 2017-06-29 |
| 17 | 201737001725-FORM-26 [12-02-2018(online)].pdf | 2018-02-12 |