An immune-related prognostic risk model for colorectal cancer was constructed based on next-generation sequencing

Abstract

Abstract Objective Screening the immune-related genes of colorectal cancer based on clinical next generation sequencing and construction of an immune-related prognostic risk model, so as to provide an immediate indicator for evaluating the prognosis and efficacy of immunotherapy of CRC patients. Methodology: Univariate and multivariate Cox risk regression analysis was used to analyze the correlation between immune-related genes, clinicopathological features, and prognosis of CRC patients, and a prognostic risk model was established. Results A total of 57 mutant genes were detected in 150 CRC patients, of which SNV and Indel had the highest mutation frequency, (92.67% and 47.33%, respectively). The genes with the highest number of mutations were TP53 and APC. In all 150 CRC patients, 12 mutation genes were detected, including 6 drug-treatable genes: KRAS, PIK3CA, PTEN, BRAF, NRAS, and TP53.TP53 and PIK3CA were the genes with the most drug-treatable mutation sites, and KRAS, NRAS, and BRAS had the highest medication grade. The mutation rates of 36 CRC common detection genes in the NGS and TCGA clinical databases were very consistent, and they were enriched in negative regulation of cell proliferation, negative regulation of apoptosis, and kinase pathways such as PI3K-AKT signaling pathway. Through the correlation analysis of immune infiltration, 14 immune-related genes TP53, JAK1, MTHFR, EGFR, KDR, APC, KRAS, TSC2, PMS2, KIT, ALK, BRAF, CTNNB1, and FBXW7 were obtained. The Cox univariate analysis and Cox multivariate analysis showed that late clinical stage (stage), late T stage and ALK gene mutation increased the risk of death and were independent prognostic factors affecting the risk of death. A Cox proportional-hazards model was constructed : h(t,x)/h0(t) = EXP(0.835 clinical stage + 0.878T + 1.094ALK). Among the 112 clinical follow-up patients, the survival time of CRC patients with high-risk scores was significantly shorter than that of CRC patients with low-risk scores. In addition, the risk score of the MSI-L group was significantly higher than that of the MSS group in the 92 CRC patients data sets of the TCGA database. Conclusion ALK gene mutation may be related to immune and prognostic survival in CRC patients; the constructed prognostic risk model can be used to evaluate the prognosis and efficacy of immunotherapy in CRC patients.