An aging-related signature predicts favorable outcome and immunogenicity in lung adenocarcinoma.

Abstract

Aging has been demonstrated to play vital roles in the prognosis and treatment efficacy of cancers, including lung adenocarcinoma (LUAD). This novel study aimed to construct an aging‐related risk signature to evaluate the prognosis and immunogenicity of LUAD. Transcriptomic profiles and clinical information were collected from a total of 2518 LUAD patients from 12 independent cohorts. The risk signature was developed by combining specific gene expression with the corresponding regression coefficients. One cohort treated with the immune checkpoint inhibitor (ICI) was also used. Subsequently, a risk signature was developed based on 21 aging‐related genes. LUAD patients with low‐risk scores exhibited improved survival outcomes in both the discovery and validation cohorts. Further immunology analysis revealed elevated lymphocyte infiltration, decreased infiltration of immune‐suppressive cells, immune response‐related pathways, and favorable ICI predictor enrichment in the low‐risk subgroup. Genomic mutation exploration indicated the enhanced mutation burden and higher mutation rates in significantly driver genes of TP53, KEAP1, SMARCA4, and RBM10 were enriched in patients with a low‐risk signature. In the immunotherapeutic cohort, it was observed that low‐risk aging scores were markedly associated with prolonged ICI prognosis. Overall, the estimated aging signature proved capable of evaluating the prognosis, tumor microenvironment, and immunogenicity, which further provided clues for tailoring prognosis prediction and immunotherapy strategies, apart from promoting individualized treatment plans for LUAD patients.