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Group of genes for molecular typing of non-hyper-mutant rectal cancer and application thereof

A technique of molecular typing and mutation type, applied in the prediction of postoperative recurrence and metastasis of rectal cancer, in the genetic field of molecular typing of non-hypermutated rectal cancer, can solve the problems of tumor recurrence or metastasis, patient death, etc. Achieve good clinical guidance and avoid over-treatment effects

Active Publication Date: 2019-12-13
ZHEJIANG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention aims at the problem that tumor recurrence or metastasis may occur in patients with rectal cancer after surgery, which eventually leads to the death of the patient, and provides a set of genes and detection kits for predicting postoperative recurrence and metastasis of non-hypermutated rectal cancer

Method used

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  • Group of genes for molecular typing of non-hyper-mutant rectal cancer and application thereof
  • Group of genes for molecular typing of non-hyper-mutant rectal cancer and application thereof
  • Group of genes for molecular typing of non-hyper-mutant rectal cancer and application thereof

Examples

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Embodiment 1

[0032] Example 1: Preparation of Genomic DNA Samples and Determination of Tumor Somatic Mutation Sites

[0033] In order to detect somatic mutations in rectal cancer, the present invention designed a gene group including 524 genes (Table 1), and customized capture probes for this gene group. Targeted sequencing of 157 rectal cancer tissue specimens was completed using this capture probe. All specimens were from surgically resected tissue specimens, and the excess part after pathological diagnosis was used for sequencing research. This work was approved by the Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine. This part of 157 tumor patients is the ZJU data set.

[0034] Table 1: List of 524 genes

[0035]

[0036]

[0037]

Embodiment 2

[0038] Example 2: Establishment of a gene mutation prognosis prediction model for non-hypermutated rectal cancer

[0039]Since hypermutated and non-hypermutated rectal cancers are quite different in their pathogenesis, prognosis and curative effect, the present invention firstly divides rectal cancer patients into hypermutated and non-hypermutated two groups. Tumors with a mutation burden rate less than or equal to 10Mut / Mb were defined as non-hypermutated tumors. Of the 157 cases of rectal cancer (ZJU data set) in Example 1, 148 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 112 cases of rectal cancer data from TGCA as independent verification data (TCGA data set), and 107 cases were determined as non-hypermutated according to the same standard rectal cancer. Further, the present invention requires patient data with a follow-up period of more than 15 month...

Embodiment 3

[0041] Example 3: Analysis of postoperative mortality risk of non-hypermutated stage III rectal cancer using a six-gene prognostic prediction model

[0042] According to the AJCC cancer staging system commonly used in clinical practice, rectal cancer can be divided into stage 0 to stage IV, and the treatment options for different stages are quite different. Therefore, the present invention analyzes the stage III rectal cancer, which is more common clinically. The results showed that the six-gene model was significantly associated with postoperative survival time in stage III rectal cancer with a hazard ratio of 3.89 (95% confidence interval = 1.88-8.02, P Figure 4 , indicating that compared with patients in the 6-gene wild-type group, patients in the 6-gene mutant group had a worse prognosis and a higher risk of death. At the same time, there was no significant difference in the proportion of patients receiving postoperative adjuvant chemotherapy between the six-gene wild grou...

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Abstract

The invention discloses a group of genes for molecular typing of non-hyper-mutant rectal cancer. The genes comprise an SMAD4 gene, an MUC16 gene, an FAT4 gene, an FLG gene, an ROBO2 gene and an NEB gene, molecular typing can be performed on rectal cancer according to the gene mutation characteristic combination, so that low-risk group patients with relatively low postoperative recurrence and deathrisks are screened, treatment can be performed according to a current postoperative adjuvant therapy scheme, and excessive treatment is avoided; and another group of high-risk group patients with higher postoperative recurrence and death risks can find better other schemes for the patients on the basis of the current postoperative adjuvant therapy scheme. The invention also discloses a kit for capturing the gene.

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 rectal cancer and the application of the group of genes in predicting postoperative recurrence and metastasis of rectal cancer. Background technique [0002] Malignant tumors have become a global public health problem. In the past thirty years, the incidence of cancer has been increasing at an average annual rate of 3%-5%, and cancer has become the first 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 standardized inciden...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12N15/11C12N15/12
CPCC12Q1/6886C07K14/82C12Q2600/118C12Q2600/156
Inventor 葛维挺白瑞胡涵光蔡文郑树
Owner ZHEJIANG UNIV
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