Abstract
BackgroundOverall 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.MethodsGene 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).ConclusionsThe TCR signaling pathway played a distinct role in the OS of these 6 cancer types.
Highlights
Overall survival (OS) is a key endpoint measure in the management of patients with cancer
High-level expression of the prognostic immune genes (PIGs) participating in the T cell receptor (TCR) signaling pathway was associated with improved OS in 5 cancer types (BRCA, Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), Head and Neck Squamous Cell Carcinoma (HNSC), Lung Adenocarcinoma (LUAD), and SARC), but with decreased OS in lower-grade glioma (LGG)
The results of this study demonstrated that the prognostic genes of 6 cancer types (BRCA, CESC, HNSC, LUAD, SARC, and LGG) correlated significantly with the immune system
Summary
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. Cancer is the leading cause of death worldwide [1,2,3]. Advances in the understanding of the molecular mechanisms of interaction between the tumor and immune system have provided new approaches to cancer treatment [5,6,7]. Immune checkpoints are regulators that play crucial roles in maintaining self-tolerance, which prevents the OS is defined as the time from entry into a clinical trial until death from any cause [10]. A large body of evidence has demonstrated that immune checkpoint therapy is correlated with improved patient OS in several
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