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Intrahepatic duct cell cancer related gene mutation targets and application thereof

A technology for inner bile duct and cell carcinoma, which is applied in the field of biotechnology and medical diagnosis, can solve the problems such as the characteristics of gene mutations are not clear, and achieve a targeted and targeted treatment that is helpful for selection and evaluation, good therapeutic effect, and Effect

Inactive Publication Date: 2015-11-18
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0006] This is the main problem at present, why there is such a problem, one of the important reasons is that the biological behavior of intrahepatic cholangiocarcinoma, especially the characteristics of gene mutations have not been clarified

Method used

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  • Intrahepatic duct cell cancer related gene mutation targets and application thereof
  • Intrahepatic duct cell cancer related gene mutation targets and application thereof
  • Intrahepatic duct cell cancer related gene mutation targets and application thereof

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Embodiment 1

[0036] Shanghai WuXi AppTec New Drug Development Co., Ltd. was entrusted to use IlluminaHiSeq2000 to analyze the whole tissue samples of 103 patients with intrahepatic cholangiocarcinoma confirmed by histopathology and their control tissues (distal tissues of cancer tissues) from Eastern Hepatobiliary Surgery Hospital of Second Military Medical University. The genome exomes were sequenced, and one patient was excluded because the number of somatic gene mutations was significantly different from other patients. The remaining 102 patients with intrahepatic cholangiocarcinoma were summarized in Table 1 for the overall exome sequencing results of the above specimens. Bioinformatics analyzed the sequencing results and found that there were significant mutations in 25 genes, including 8 genes, namely TP53 (p=0.0001), KRAS (p=0.004), IDH1 (p=0.00019), PTEN (p=0.0078) ), ARID1A (p=0.00449), EPPK1 (p=0.00486), ECE2 (p=0.0357) and FYN (p=0.00258) may be the driver genes (see Table 2).

...

Embodiment 2

[0046] The whole genome exomes of 102 patients with intrahepatic cholangiocarcinoma and their control tissues were sequenced and analyzed, and it was found that P53 gene mutation mainly occurred in serum HBsAg-positive intrahepatic cholangiocarcinoma (61.54%) (see Table 3). .

[0047] Table 3: Correlation analysis of P53 mutation and clinicopathological features of intrahepatic cholangiocarcinoma

[0048] (ComparisonofclinicopathologicalfeaturesofICCpatientsaccordingtop53mutation)

[0049]

[0050]

[0051] *:numberofavailabledata;ICC:intrahepaticcholangiocarcinoma;HBV:hepatitisBvirus;M:male;F:female;TBIL:totalbilirubin;ALT:alanineaminotransferase;AST:aspartateaminotransferase;andAFP:Alpha-fetoprotein;ALP:alkalinephosphatase;r-GT:r-glutamyltransferase; CA19-9:carbohydrateantigen19-9;CK:cytokeratin.

[0052] KRAS gene mutation is basically the only one found in serum HBsAg-negative intrahepatic cholangiocarcinoma rate (29.6%) (see Table 4).

[0053] Table 4: Correlatio...

Embodiment 3

[0059] Bioinformatics analysis of the sequencing results found that three signal transduction pathways, namely Ras / PI3K signaling pathway, p53 / cellcycle signaling pathway and TGF-b / SMAD signaling pathway, are very likely to be related to the occurrence and development of intrahepatic cholangiocarcinoma ( Figure 4 a is the relationship between Ras / PI3K signaling pathway and the occurrence and development of intrahepatic cholangiocarcinoma; Figure 4 b is the relationship between p53 / cellcycle signaling pathway and the occurrence and development of intrahepatic cholangiocarcinoma; Figure 4 c is the relationship between the TGF-b / SMAD signaling pathway and the occurrence and development of intrahepatic cholangiocarcinoma), about 75% of the patients have mutations in the p53 / cellcyclesignaling and Ras / PI3Ksignaling signaling pathways.

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Abstract

The invention relates to the fields of biotechnology and medical diagnosis, and concretely relates to intrahepatic duct cell cancer related gene mutation targets and an application of the gene mutation targets in reagents or kits for diagnosing or treating intrahepatic duct cell cancer and assessing intrahepatic duct cell cancer prognosis. The intrahepatic duct cell cancer related gene mutation targets TP53, KRAS, IDH1, PTEN, ARID1A, EPPK1, ECE2 and FYN are found in the invention, and the gene mutation targets can be effectively used in development judgment, treatment scheme selection and / or prognosis assessment of the intrahepatic duct cell cancer, so a new intrahepatic duct cell cancer diagnosis agent and / or treatment agent are / is provided for the fields, and have / has certain clinic application prospect.

Description

technical field [0001] The present invention relates to the fields of biotechnology and medical diagnosis, in particular to intrahepatic cholangiocarcinoma-related gene mutation targets, and reagents for diagnosing or treating intrahepatic cholangiocarcinoma and evaluating the prognosis of intrahepatic cholangiocarcinoma by these gene mutation targets. or application in the kit. Background technique [0002] Primary liver cancer (liver cancer) is one of the major diseases endangering human health. Currently, the incidence rate per 100,000 people in the world is about 0.85, and the growth rate is 165% in the past 30 years. The incidence of liver cancer in Asians, including China, is the highest in the world. About 56% of liver cancer occurs in China, and the incidence and growth rate of 100,000 people are much higher than the world average. [0003] Primary liver cancer mainly includes hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcin...

Claims

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Application Information

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IPC IPC(8): C12N15/11C12Q1/68
Inventor 胡和平陈楠生丁传凡周华邦李嘉睿邹姗姗蒋晓兰汪慧李玉琼
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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