A systematic analysis of immune genes and overall survival in cancer patients

Abstract

BACKGROUND: Overall survival (OS) is a key endpoint measure in the management of patients with cancer. Immunotherapy has become a dominant strategy in cancer therapy. To investigate the relationship between OS and the immune system, we assessed the role of immune genes in OS in 8648 patients across 22 cancer types. METHODS: Gene expression data and clinical information were collected from The Cancer Genome Atlas (TCGA) and cBioPortal. Survival analysis was performed with a Cox proportional hazards regression model. RESULTS: (1) The number of prognostic genes, prognostic immune genes (PIGs) and the hazard ratio (HR) of PIGs in different cancer types all varied greatly; (2) KEGG pathway enrichment analyses indicated that the prognostic genes of 6 cancer types were significantly enriched in multiple (≥5) immune system-related pathways. Of the PIGs in these 6 cancer types, we screened 48 common PIGs in at least 5 cancer types. Eleven out of the 48 PIGs were found to participate in the T cell receptor (TCR) signaling pathway according to the STRING database. Among these genes, ZAP70, CD3E, CD3G, CD3D, and CD247 were part of the TCR 'signal-triggering module'; (3) High expression of the PIGs involved in the TCR signaling pathway was associated with improved OS in 5 cancer types (breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD), and sarcoma (SARC)), but was associated with decreased OS in brain lower-grade glioma (LGG). CONCLUSIONS: The TCR signaling pathway played a distinct role in the OS of these 6 cancer types.