A Risk Model Based on Immune-Related Genes Predicts Prognosis and Characterizes the Immune Landscape in Esophageal Cancer

Abstract

Aberrant immune gene expression has been shown to have close correlations with the occurrence and progression of esophageal cancer (EC). We aimed to generate a prognostic signature based on immune-related genes (IRGs) capable of predicting prognosis, immune checkpoint gene (ICG) expressions, and half-inhibitory concentration (IC₅₀) for chemotherapy agents for EC patients. Transcriptome, clinical, and mutation data on tumorous and paratumorous tissues from EC patients were collected from The Cancer Genome Atlas (TCGA) database. Then, we performed differential analysis to identify IRGs differentially expressed in EC. Their biofunctions and related pathways were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These gene expression profiling data were merged with survival information and subjected to univariate Cox regression to select prognostic genes, which were then included in a Lasso-Cox model for signature generation (risk score calculation). Patients were divided into the high- and low-risk groups using the median risk score as a cutoff. The accuracy of the signature in overall survival prediction was assessed, so were its performances in predicting ICG expressions and IC₅₀ for chemotherapy and targeted therapy agents and immune cell landscape characterization. Fifteen prognostic IRGs were identified, seven of which were optimal for risk score calculation. As expected, high-risk patients had worse overall survival than low-risk individuals. Significant differences were found in tumor staging, immune cell infiltration degree, frequency of tumor mutations, tumor mutation burden (TMB), and immune checkpoint gene expressions between high- vs. low-risk patients. Further, high-risk patients exhibited high predicted IC₅₀ for paclitaxel, cisplatin, doxorubicin, and erlotinib compared to low-risk patients. The seven-IRG-based signature can independently and accurately predict overall survival and tumor progression, characterize the tumor immune microenvironment (TIME) and estimate ICG expressions and IC₅₀ for antitumor therapies. It shows the potential of guiding personalized treatment for EC patients.

Keywords: chemotherapy; esophageal cancer; immune-related genes; immunotherapy; prognosis; risk model.