Comprehensive characterization of the senescence gene Klotho in lung adenocarcinoma

Abstract Background Aging has become an important mechanism and target for lung diseases. We aimed to explore novel aging markers for lung adenocarcinoma (LUAD) that may partially modulate immune responses. Methods Aging-related gene sets were acquired from HAGR and Ageing Atlas databases. We retrieved RNA-seq expression and clinical data of LUAD from TCGA and three GEO cohorts. Candidate differentially expressed genes (DEGs) were selected by univariate COX, LASSO COX and multivariate COX regression to construct the prognostic model and nomogram. The ssGSEA, GO terms and KEGG pathway analysis were employed for functional enrichment. The Wilcoxon test and Kaplan-Meier method were applied for differences in distribution and prognosis, respectively. The Spearman method was performed for the correlations between KL expression and CPG site methylation, m6A modifications and immunological characteristics. Results We identified a four-gene prognostic panel of LUAD to construct a nomogram with C-index of 0.721, screening KL out as one prospective senescence gene. Low-expressed KL independently contributed to a poor prognosis for LUAD patients, which may be partially mediated by hypermethylation and m6A modification. Functional enrichment revealed the involvement of immune pathways, further proved by the positive correlation between KL expression and immune scores, abundance of immune infiltrating cells, and immunological characteristics. High-expressed KL gene in decreased immune cell subgroups (CD4 + memory T cells, Eosinophils, NK cells, et al) had a better prognosis. Conclusion Immune-related KL gene was a potent predictor of LUAD, suggesting that further exploration of KL as a therapeutic agent may break the bottleneck in LUAD treatment.