Identification of a Cancer Testis Antigen-Associated Six-Gene Signature in Lung Adenocarcinoma for the Prediction of Survival and Response to Immune-Checkpoint Inhibitors

Abstract

Abstract Background Lung cancer is a leading cause of cancer-related deaths, with lung adenocarcinoma (LUAD) being one of the major types of lung cancer. A limited number of studies have revealed that cancer testis antigens (CTAs) could serve as prognostic indicators for LUAD patients. Methods In this bioinformatics study, we constructed a novel CTA-related gene signature that predicted survival and responses to immune-checkpoint inhibitors (ICIs) in patients with LUAD, and exploited univariate and Lasso-Cox regression analyses to evaluate the mechanisms underlying the signature’s prognostic capability. Immune cell infiltration, tumor mutation burden (TMB), and immunophenoscores (IPSs) related to the prognostic signature in LUAD with different risk scores were thoroughly explored. Results Our prognostic signature was based upon six CTAs, and multivariate analysis showed that the six-CTA signature was an independent prognostic factor in overall survival for patients with LUAD. Memory resting CD4 T cells, monocytes, dendritic resting cells, and resting mast cells were elevated in the six-CTA signature high-risk group, and M0 macrophages and activated mast cells were reduced relative to the low-risk group. The six-CTA signature low-risk group possessed a higher IPS, and was more sensitive to an immune-checkpoint inhibitor (ICI)—representing a more immunogenic phenotype. Conclusion In summary, we herein established a six-CTA prognostic signature for predicting survival in patients with LUAD and their potential responses to immunotherapy.