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A set of genes for molecular typing of non-hypermutated rectal cancer and their applications

A molecular typing and mutation technology, applied in the biological field, can solve the problems of tumor recurrence or metastasis, patient death, etc., achieve good clinical significance, and avoid the effect of excessive treatment.

Active Publication Date: 2022-07-08
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] 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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  • A set of genes for molecular typing of non-hypermutated rectal cancer and their applications
  • A set of genes for molecular typing of non-hypermutated rectal cancer and their applications
  • A set of genes for molecular typing of non-hypermutated rectal cancer and their applications

Examples

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Effect test

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 rectal cancer, the present invention designed a gene group including 524 genes (Table 1), and customized the capture probe for this gene group. Targeted sequencing of 157 rectal cancer tissue samples was completed using this capture probe. All specimens were obtained from surgically resected tissue specimens from patients, and the excess after pathological diagnosis was used for sequencing studies. This work was approved by the Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine. This part of the 157 tumor patients is the ZJU dataset.

[0032] Table 1: List of 524 genes

[0033] ABCA13 ASPM C20orf54 COL6A3 EIF3E FAT4 HEMGN LCORL ABCA6 ATAD5 C2orf44 COL6A6 EIF4A2 FBN2 HIST1H2BC LEKR1 ABCA8 ATM C9 CRB1 ELF3 FBXW7...

Embodiment 2

[0034] Example 2: Establishment of a gene mutation prognosis prediction model for non-hypermutated rectal cancer

[0035] Because the occurrence mechanism, prognosis and curative effect of hypermutated and non-hypermutated rectal cancers are quite different, the present invention firstly divides rectal cancer patients into two groups: hypermutated and non-hypermutated. Tumors with a mutation load rate of less than or equal to 10 Mut / Mb were defined as non-hypermutated tumors. Of the 157 rectal cancers in Example 1 (ZJU dataset), 148 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), of which 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 time of more than 15 month...

Embodiment 3

[0037] Example 3: Analysis of postoperative mortality risk of non-hypermutated stage III rectal cancer using a six-gene prognostic prediction model

[0038] 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 plans of different stages are quite different. Therefore, the present invention analyzes the clinically more common stage III rectal cancer respectively. The results showed that the six-gene model was significantly associated with postoperative survival in stage III rectal cancer with a hazard ratio of 3.89 (95% confidence interval = 1.88-8.02, P 0.001), see Figure 4 , indicating that patients in the 6-gene mutant group had a worse prognosis and a higher risk of death compared with patients in the 6-gene wild-type group. At the same time, there was no significant difference in the proportion of patients receiving postoperative adjuvant chemotherapy between the six-gene ...

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Abstract

The invention discloses a group of genes for molecular typing of non-hypermutated rectal cancer, including SMAD4 gene, MUC16 gene, FAT4 gene, FLG gene, ROBO2 gene and NEB gene; rectal cancer can be classified according to the combination of the gene mutation characteristics. Molecular typing to screen low-risk patients with a lower risk of postoperative recurrence and death, who can be treated according to the current postoperative adjuvant therapy regimen to avoid overtreatment; while another group of patients with a higher risk of postoperative recurrence and death For patients in the high-risk group, better alternatives can be found based on the current postoperative adjuvant therapy. The present 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 rectal cancer, and the application of the group of genes in predicting the recurrence and metastasis of rectal cancer after operation. Background technique [0002] Surgery, chemotherapy and radiotherapy are traditional cancer treatments. At present, most early stage patients can get better prognosis after comprehensive treatment, but these treatments cannot reduce the mortality of all cancer patients. The main reason is tumor recurrence or metastasis after surgical treatment, which eventually leads to the death of patients. In current clinical practice, standard adjuvant chemotherapy is recommended for all stage III colorectal cancers, generally a combination regimen containing oxaliplatin, which is adjusted by clinicians according to the specific situation of the patient. However, the prognosis of patients with the same ...

Claims

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Application Information

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Patent Type & Authority Patents(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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