Marker, kit and device for predicting sensitivity of colorectal cancer patients to immunotherapy

An immunotherapy, colorectal cancer technology, applied in the field of cancer, can solve the problems of immunotherapy efficacy deficiency, long working cycle, high technical platform requirements, and achieve the effect of expanding the potential benefit population and reducing the cost of testing

Pending Publication Date: 2022-01-21
SHANGHAI ORIGIMED CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, TMB detection has high requirements on the technical platform, long working cycle, and high sequencing cost
[0006] Therefore, MSI and TMB as existing biomarkers to predict the efficacy of immunotherapy in patients with colon adenocarcinoma still have certain defects

Method used

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  • Marker, kit and device for predicting sensitivity of colorectal cancer patients to immunotherapy
  • Marker, kit and device for predicting sensitivity of colorectal cancer patients to immunotherapy
  • Marker, kit and device for predicting sensitivity of colorectal cancer patients to immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] Download the data of 85 patients with advanced colon adenocarcinoma (COAD) who received immune checkpoint inhibitor therapy from the MSKCC data, which includes gene mutation data, treatment regimen data and overall survival (OS) data, as shown in Table 1 Show.

[0090]

[0091]

[0092]

[0093]

[0094]

[0095] First, univariate COX analysis was performed on 85 patients with advanced colon adenocarcinoma (COAD) receiving immune checkpoint inhibitor therapy, and it was found that the genes most correlated with overall survival (OS) of immunotherapy (P<0.1) were shared among 85 patients. 6, the specific information is shown in Table 2.

[0096] Table 2

[0097]

[0098] These 6 genes were then divided into two categories: among them, APC and VHL were preliminarily judged as negatively correlated factors for predicting overall survival because the HR value was greater than 1 (but there was only one case of VHL mutant type, so it was difficult to judge ...

Embodiment 2

[0105] In order to further verify that the APC gene and FAT1 gene of the present invention are independent predictive risk factors for the efficacy of immunotherapy, the present invention downloads the data of 619 patients with advanced colon adenocarcinoma (COAD) in the DFCI public database, which includes gene mutation data, clinical And survival data, among them, 529 patients had MSI detection results, and found that the somatic mutation status of APC+FAT1 gene was significantly correlated with MSI and TMB status, as shown in Table 3, Table 4 and Table 5.

[0106] table 3

[0107]

[0108] Table 4

[0109] group MSS MSI MSI ratio GS=0 264 21 7.4％ GS=1 174 70 28.7％

[0110] table 5

[0111] group TMB-High TMB-Low TMB-High Ratio GS=0 25 302 7.1％ GS=1 89 203 30.5％

[0112] The samples with somatic mutation in APC gene were classified as APC=1 group; otherwise, the samples without any somatic mutation...

Embodiment 3

[0117] This embodiment provides a method for predicting the sensitivity of colorectal cancer patients to immunotherapy, comprising the following steps:

[0118] S1: Obtain the clinicopathological information of the subject, and determine whether the subject is a patient with advanced colon adenocarcinoma;

[0119] S2: If the subject is a patient with advanced colon adenocarcinoma, obtain the mutation data of the subject's APC and FAT1 genes, and judge whether there are mutations in the APC gene and the FAT1 gene based on the mutation data;

[0120] S3: If there is a mutation in the APC gene and there is no mutation in the FAT1 gene, calculate GS=0, otherwise calculate GS=1;

[0121] S4: Output the prediction result of the subject's sensitivity to immunotherapy according to the GS score, output the prediction result of the subject's sensitivity to immune checkpoint inhibitor therapy when GS=1, and output the prediction result of the subject's sensitivity to immune checkpoint in...

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Abstract

The invention relates to a gene marker combination for predicting sensitivity of colorectal cancer patients to immunotherapy. The gene marker combination comprises an APC gene and an FAT1 gene. Wherein mutation states of the APC gene and the FAT1 gene have significant correlation with microsatellite instability (MSI) and tumor mutational burden (TMB) states, and the APC gene and the FAT1 gene can be used as new biomarkers to predict the sensitivity of the colorectal cancer patients to immunotherapy and predict the effectiveness of the immunotherapy in colorectal cancer patients. Compared with TMB which needs to detect at least hundreds of genes for calculation, the gene marker combination disclosed by the invention, as a biomarker, can predict the immunotherapy effect only by detecting mutations of a small number of key genes, so that the detection cost is greatly reduced; compared with MSI, the gene marker combination can cover more people according to gene detection and expand potential beneficiaries of immunotherapy.

Description

technical field [0001] The present invention relates to the technical field of cancer, in particular to a marker, a kit and a device for predicting the sensitivity of colorectal cancer patients to immunotherapy. Background technique [0002] Colorectal cancer (CRC), also known as colorectal cancer, rectal cancer, colorectal cancer, colorectal cancer, or bowel cancer, is a cancer that originates from the colon or rectum (which is part of the large intestine). One of the most common malignant tumors in humans. Among them, colon adenocarcinoma is a common malignant tumor of the digestive tract derived from colonic glandular epithelium, and it is a relatively common subtype of colorectal cancer. At present, chemotherapy and / or radiotherapy are the main treatment methods for advanced colon adenocarcinoma, but these treatment methods have strong side effects and are prone to drug resistance. [0003] In recent years, immune checkpoint inhibitors (Immune Checkpoint Inhibitors, IC...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G16B30/00G16B20/50
CPCC12Q1/6886G16B30/00G16B20/50C12Q2600/106C12Q2600/156
Inventor 尤冬张昭
Owner SHANGHAI ORIGIMED CO LTD
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