A panel of genes for molecular typing of non-hypermutated colorectal cancer and its application

A technology of hypermutated nodal and molecular typing, applied to the prediction of postoperative recurrence and metastasis of colorectal cancer, the genetic field of molecular typing of non-hypermutated colorectal cancer, can solve tumor recurrence or metastasis, patients Death and other issues, achieve good clinical guidance, strengthen monitoring, and avoid over-treatment effects

Active Publication Date: 2021-04-20
ZHEJIANG UNIV
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

[0005] Aiming at the problem that tumor recurrence or metastasis may occur in patients with colorectal cancer after surgery, which eventually leads to the death of the patient, the present invention provides a set of genes and detection kits for predicting postoperative recurrence and metastasis of non-hypermutated colorectal cancer

Method used

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  • A panel of genes for molecular typing of non-hypermutated colorectal cancer and its application
  • A panel of genes for molecular typing of non-hypermutated colorectal cancer and its application
  • A panel of genes for molecular typing of non-hypermutated colorectal cancer and its application

Examples

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Embodiment 1

[0030] Example 1 Preparation of Genomic DNA Samples and Determination of Tumor Somatic Mutation Sites

[0031] In order to detect the somatic mutation of colorectal cancer, the present invention completed the high-throughput sequencing of 338 colorectal cancer tissue samples in two stages, and completed the high-throughput sequencing of 80 cases of colorectal cancer in the first stage, of which 10 cases For whole genome sequencing, 70 cases for whole exome sequencing. Through the first stage of high-frequency gene analysis, further combining the high-frequency genes in the TCGA database and COSMIC database, and the NCCN guidelines for the diagnosis and treatment of hereditary colorectal cancer, the present invention designed a gene group comprising 524 genes (Table 1), Capture probes targeting this gene group were customized for the second stage of sequencing. In the second phase, the targeted sequencing of 258 colorectal cancer tissue samples was completed using the capture ...

Embodiment 2

[0036] Example 2 Establishment of a gene mutation prognosis prediction model for non-hypermutated colorectal cancer

[0037] Since there are great differences in the pathogenesis, prognosis, and curative effect of hypermutated and non-hypermutated colorectal cancer, the present invention firstly divides colorectal cancer patients into two groups: hypermutated and non-hypermutated. Tumors with a mutation burden rate less than or equal to 10Mut / Mb were defined as non-hypermutated tumors. Of the 338 cases of colorectal cancer (ZJU data set) in Example 1, 293 cases were determined to be non-hypermutated. In addition, in order to verify the stability and universality of the model, the present invention downloaded a total of 382 cases of colorectal cancer data from TGCA as independent verification data (TCGA data set), and 319 cases were determined as non-hypermutated according to the same standard type colorectal cancer. Further, the present invention requires patient data with a...

Embodiment 3

[0039] Example 3 Application of 5-gene prognostic prediction model to analyze postoperative recurrence and metastasis of nodal non-hypermutated rectal cancer

[0040] Since the main cause of death of tumor patients is recurrence and metastasis, and the main factor affecting prognosis is also recurrence and metastasis, so the present invention analyzes the correlation between the mutation status of 5 genes and recurrence and metastasis. In order to exclude the influence of residual tumor factors on the patient's prognosis, the present invention selects colorectal cancer patients whose tumors have been completely resected. According to the mutation characteristics of the 5 genes, patients are divided into mutant type and wild type, and survival analysis and comparison of disease-free survival time can prove that the recurrence risk of mutant type patients is significantly higher than that of wild type patients, with a hazard ratio of 2.01 (95% confidence interval =1.33‐3.04, P F...

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Abstract

The invention discloses a group of genes used for molecular typing of non-hypermutated colorectal cancer, including COL6A3 gene, FLG gene, LRP1B gene, MUC16 gene and SMAD4 gene; colorectal cancer can be molecularly classified according to the combination of gene mutation characteristics Classification, to screen patients with a higher possibility of recurrence and metastasis after surgery, and clinicians can strengthen monitoring and treatment of such patients; while another group of patients with a lower possibility of recurrence and metastasis after surgery can strengthen observation, Avoid overtreatment. The invention also discloses a kit for capturing the above-mentioned genes.

Description

technical field [0001] The invention belongs to the field of biotechnology, and relates to a group of genes used for molecular typing of non-hypermutated colorectal cancer, and the application of the group of genes in predicting postoperative recurrence and metastasis of colorectal cancer. Background technique [0002] Malignant tumors have become a global public health problem. In the past three decades, the incidence of cancer has been increasing at an average annual rate of 3%-5%, and cancer has become the number one cause of death for human beings. Colorectal cancer is one of the common cancers in my country. In recent decades, the incidence rate of colorectal cancer has increased by an average of 3% to 4% per year, but there are large regional differences. For example, the incidence rate in Shanghai in 2012 reached 56 / 100,000. The Globocan 2012 published by the International Agency for Research on Cancer (IARC) of the World Health Organization estimates that the stand...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886C12N15/11
CPCC12Q1/6886C12Q2600/118
Inventor 葛维挺
Owner ZHEJIANG UNIV
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