Alternative splicing of immune-related genes predicts the outcome in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is one of the most fatal cancers, and more studies are needed fora better understanding of this disease. Studies have reported that alternative splicing (AS) in cancershas important prognostic value. Therefore, this study aimed to determine the correlation between theAS events of immune-related genes and LUAD prognosis. The gene expression matrix and clinicalinformation of patients with LUAD were downloaded from The Cancer Genome Atlas database.Univariate and multivariate Cox regression analyses were used to screen the differentially expressedAS (DEAS) events of immune-related genes related to prognosis. A protein-protein interactionnetwork was constructed using the abovementioned genes, and enrichment analysis was performed.Finally, we analyzed the regulatory relationship between DEAS events and AS factors and analyzedthe prognostic subtypes via cluster analysis. A total of 188 out of 2,227 immune-related AS events(111 of 373 immune-related genes) were significantly (p > 0.05) associated with the overall survival(OS) of patients with LUAD. Three AS types, namely alternate promoter, retained intron, and exonskip, significantly distinguished high-risk patients from low-risk patients. Further analysis revealedthat the alternatively spliced immune genes were involved in the activation of the immune responseas well as in cytokine production and signaling and that the AS events were highly correlated withsplicing factors. Finally, the immune-related genes were subgrouped into four clusters, with eachcluster differently predicting the OS of patients with LUAD. In summary, AS events in immunegenes are novel prognostic factors for LUAD and imply dysregulated AS in the immune system andabnormal antitumoral immune responses