Construction of a new tumor immunity-related signature to assess and classify the prognostic risk of colorectal cancer

Abstract

Purpose: Although immunotherapy and checkpoint inhibitors contribute to the treatment of colorectal cancer (CRC), few patients can benefit from these treatments. Therefore, our goal was to develop a marker based on immune-related genes to predict the prognosis of patients with CRC to guide treatment strategies. Methods: Gene expression data from colorectal cancer patients in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas were analyzed systematically. We used Cox regression to identify immune-related genes with potential prognostic value. The expression of immune genes, infiltration level of immune cells, and several immune-related molecules were further compared between the high-risk and low-risk groups. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used for functional analysis. Results: Five GEO datasets were integrated into a merged GEO dataset, which showed obvious survival in StromalScore and ESTIMATEScore. WGCNA showed that 749 genes of the pink module are related to immunity, 95 of which are related to prognosis, correlating with cytokine– cytokine receptor interaction and natural killer cell-mediated cytotoxicity. Among these genes, an 11-gene signature was developed through stability selection and LASSO Cox regression. Univariate and multifactorial Cox regression analyses demonstrated that gene signature was an independent prognostic factor for predicting survival in patients with colorectal cancer. Samples from the low-risk group may be more sensitive to immunotherapy. In addition, the nomogram risk prediction model effectively predicted the prognosis of CRC patients by appropriately stratifying the risk scores. Conclusion: In conclusion, we developed a novel immune-related gene signature that may be useful in predicting cancer progression and prognosis, thus contributing to the individualized management of colorectal cancer patients.