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Gene sets, scoring models and their applications for assessing the tumor microenvironment

A tumor microenvironment and gene set technology, applied in the field of bioinformatics, can solve the problems of incomplete immunotherapy mechanism, low response rate, poor stability, etc., achieving significant prediction effect, saving medical resources, and better efficacy Effect

Active Publication Date: 2022-05-10
广东隆宇医疗科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the stability of various biomarkers in predicting the curative effect of PD-1 / PD-L1 monoclonal antibody is not good at present, and they all focus on the intrinsic characteristics of the tumor with obvious heterogeneity, which has certain limitations and ignores the influence of the tumor microenvironment. The evaluation of immunotherapy is not comprehensive in terms of the mechanism of action of immunotherapy, which partly explains the low response rate of gastric cancer to checkpoint inhibitors in clinical trials of multiple biomarkers; therefore, more accurate biological Markers used to predict the efficacy of immune checkpoint inhibitor PD-1 / PD-L1 monoclonal antibody

Method used

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  • Gene sets, scoring models and their applications for assessing the tumor microenvironment
  • Gene sets, scoring models and their applications for assessing the tumor microenvironment
  • Gene sets, scoring models and their applications for assessing the tumor microenvironment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 Multi-gene scoring model of tumor microenvironment of the present invention and its construction method

[0063] A method for constructing a multi-gene scoring model for evaluating tumor microenvironment includes the following steps:

[0064] (1) standardized data of Affymetrix chip of 300 patients with gastric cancer; Said data originated from GSE62254 (obtained from NCBI public database);

[0065] (2) evaluating the components of immune cells in tumor microenvironment by using CIBERSORT and MCP-counter algorithm to obtain the components evaluation results of 23 immune cells;

[0066] (3) Unsupervised clustering of immune cells in tumor microenvironment was carried out by consensuclusterplus2 to obtain different tumor microenvironment types;

[0067] (4) Through pairwise difference analysis and random forest dimensionality reduction, 244 gene sets that can evaluate tumor microenvironment scores were finally determined;

[0068] (5) In order to further realize the...

Embodiment 3

[0090] Example 3 Evaluation of the Efficacy of Tumor Microenvironment Scoring Model in Predicting the Prognosis of Patients

[0091] The above tumor microenvironment scoring system is applied to a number of gastric cancer patient queues with survival data, and the prognostic value of tumor microenvironment is analyzed. The steps are as follows:

[0092] ① Get the transcriptome chip data of gastric cancer patients from the website (https: / / www.ncbi.nlm.nih.gov / geo / ) (GSE84437, GSE15459, GSE34942, GSE57303, GSE6254), We downloaded the patient's original chip data and standardized and corrected the data by affy (Ref. 14: L. Gautier, L. Cope, B. M. Bolstad, R. A. Irizarry, AFFY-analysis of affymetrix gene chip data at the probe level. Bioinformatics 20, 307-315 (2004

[0093] ② The data of 44 tumor microenvironment genes in the gene expression matrix were extracted, and after Z-score transformation (standardized as data with mean value of 0 and standard deviation of 1), the tumor immu...

Embodiment 4

[0097] Example 4 Evaluation of Efficacy of Tumor Microenvironment Scoring Model in Predicting Immunotherapy Response of Tumor Patients

[0098] To verify the efficacy of TMEscore_plus in predicting immunotherapy, the steps are as follows:

[0099] ① Download the second-generation RNAseq sequencing data of PRJEB25780 (https: / / www.ebi.ac.uk / ENA / browser / view / PRJEB25780), and standardize the data of samples by TPM;

[0100] ② The data of 44 tumor microenvironment genes in gene expression matrix are extracted, and the sample data are standardized, so that the mean value of each gene is 0 and the standard deviation is 1, and the expression matrix is assigned to eset objects in R;

[0101] ③ Install the TMEscore R package, and use the following code to calculate the tumor microenvironment score:

[0102] # install TMEscore package

[0103] devtools::install_github("DongqiangZeng0808 / TMEscore")

[0104] # Load R package

[0105] library('TMEscore')

[0106] # Enter the gene expression mat...

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Abstract

The invention discloses a gene set for evaluating tumor microenvironment, a scoring model and an application thereof, and belongs to the field of biological information. The first use of the present invention proves that there are significant tumor microenvironment types in gastric cancer, and the prognosis of gastric cancer patients with different types is significantly different. The present invention provides a method for constructing a multigene scoring model for evaluating the tumor microenvironment of gastric cancer, and screens out 44 gene sets that can represent different microenvironment types, and the tumor microenvironment multigene scoring model corresponding to the gene set Compared with other existing models, the predictive performance is significantly better. This model is not only a prognostic marker for gastric cancer patients, but also has a significant predictive effect in pan-cancer. By effectively evaluating the tumor microenvironment, the model of the present invention can not only be used as a good prognostic biomarker, but also can predict the immunotherapy response of checkpoint inhibitors of various tumors. For better screening of immunotherapy benefit groups, It has important significance and clinical application value.

Description

Technical field [0001] The invention belongs to the field of biological information, and relates to a gene set for evaluating tumor microenvironment, a scoring model and applications thereof. technical background [0002] The incidence and mortality of gastric cancer are very high in China. There are about 400,000 new cases in China every year, accounting for 42% of the total cases in the world. In addition, advanced gastric cancer patients are common in China, and the mortality rate ranks third among all tumors. There are many prognostic factors for gastric cancer. Patients with the same clinical stage and histological grade receive the same treatment plan, and their prognosis may be different. In recent years, immunotherapy, represented by immune checkpoint inhibitors, has broken the situation that chemotherapy and targeted therapy monopolized the treatment of gastric cancer in the past, and significantly improved the survival benefits of some gastric cancer patients. However, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G16B5/00G16B30/00G16B40/00C12Q1/6886
CPCG16B5/00G16B30/00G16B40/00C12Q1/6886C12Q2600/158C12Q2600/118C12Q2600/106C12Q2600/112
Inventor 廖旺军曾东强
Owner 广东隆宇医疗科技有限公司
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