Gene sets and scoring model for evaluating tumor microenvironment, and application of gene sets

A tumor microenvironment and gene set technology, applied in the field of bioinformatics, can solve the problems of neglect of evaluation, low response rate, and incomplete mechanism of immunotherapy.

Active Publication Date: 2020-12-25
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 and scoring model for evaluating tumor microenvironment, and application of gene sets
  • Gene sets and scoring model for evaluating tumor microenvironment, and application of gene sets
  • Gene sets and scoring model for evaluating tumor microenvironment, and application of gene sets

Examples

Experimental program
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Effect test

Embodiment 1

[0062] Example 1 The multigene scoring model of the tumor microenvironment of the present invention and its construction method

[0063] A method for constructing a polygene scoring model for evaluating the tumor microenvironment, the steps are as follows:

[0064] (1) Affymetrix chip normalized data of 300 patients with gastric cancer; the data is derived from GSE62254 (obtained from NCBI public database);

[0065] (2) Evaluate the composition of immune cells in the tumor microenvironment on the sequencing data through CIBERSORT and MCP-counter algorithms, and obtain the composition evaluation results of 23 kinds of immune cells;

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

[0067] (4) Through pairwise difference analysis and random forest dimension reduction, 244 gene sets that can evaluate the tumor microenvironment score are finally determined;

[0068] (5)...

Embodiment 3

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

[0091] The above-mentioned tumor microenvironment scoring system was applied to multiple gastric cancer patient cohorts with survival data, and the prognostic value of the tumor microenvironment was analyzed. The steps are as follows:

[0092] ① Obtain the transcriptome microarray data (GSE84437, GSE15459, GSE34942, GSE57303, GSE62254) of gastric cancer patients from the website (https: / / www.ncbi.nlm.nih.gov / geo / ), we downloaded the original microarray data of the patients and Use affy to standardize and correct the data (Reference 14: L.Gautier, L.Cope, B.M.Bolstad, R.A. Irizarry, affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20, 307-315 (2004));

[0093] ② Extract the data of 44 tumor microenvironment genes in the gene expression matrix, and calculate the tumor immune score, tumor interstitial score and For the tumor microe...

Embodiment 4

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

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

[0099] ① Download the RNAseq next-generation sequencing data of PRJEB25780 (https: / / www.ebi.ac.uk / ena / browser / view / PRJEB25780), and use the TPM method to standardize the sample data;

[0100] ② Extract the data of 44 tumor microenvironment genes in the gene expression matrix, and standardize the sample data so that the mean value of each gene is 0 and the standard deviation is 1, and assign the expression matrix to the eset object in R;

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

[0102] #Install the TMEscore package

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

[0104] #load the R package

[0105] library('TMEScore')

[0106] #Enter the ge...

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Abstract

The invention discloses gene sets and a scoring model for evaluating a tumor microenvironment, and application of the gene sets, and belongs to the field of biological information. It is proved for the first time that the gastric cancer has remarkable tumor microenvironment typing, and prognosis difference of gastric cancer patients with different typing is remarkable. According to a constructionmethod of the multi-gene scoring model for evaluating the gastric cancer tumor microenvironment, 44 gene sets capable of representing different microenvironment types are screened out, and the prediction efficiency of the tumor microenvironment multi-gene scoring model corresponding to the gene sets is remarkably better than that of other existing models; and the model is not only a prognostic marker of a gastric cancer patient, but also has a quite remarkable prediction effect in pan-cancer. The model provided by the invention not only can be used as a good prognosis biomarker, but also can be used for predicting checkpoint inhibitor immunotherapy response of various tumors by effectively evaluating the tumor microenvironment, and has important significance and clinical application valuefor better screening immunotherapy benefiting people.

Description

technical field [0001] The invention belongs to the field of biological information, and relates to a gene set for assessing tumor microenvironment, a scoring model and applications thereof. Background technique [0002] The morbidity and mortality of gastric cancer in China are very high. There are about 400,000 new cases in my country every year, accounting for 42% of the total number of cases in the world. Moreover, gastric cancer patients in China are more common in advanced stages, and the death rate ranks third among all tumors. bit. There are many prognostic factors for gastric cancer. Gastric cancer patients with the same clinical stage and histological grade receive the same treatment plan, and their prognosis may also be different. In recent years, immunotherapy, represented by immune checkpoint inhibitors, has broken the monopoly of previous chemotherapy and targeted therapy in the treatment of gastric cancer, and significantly improved the survival benefits of so...

Claims

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Application Information

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Patent Type & Authority Applications(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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