Senescence gene expression in clear cell renal cell carcinoma: Role of tumor immune microenvironment and senescence-associated survival prediction

Abstract

Clear cell renal cell carcinoma (ccRCC) constitutes the most prevalent histopathologic subtype of renal cell carcinoma. The interplay between aging and cancer is complicated, and we provide a relatively new set of senescence genes that has not yet been used in the study of clear cell renal cell carcinoma. Our objective is to investigate the involvement of senescence in the development and diagnosis of ccRCC. RNA-seq and clinical data for ccRCC was obtained from the cancer genome atlas and gene expression omnibus databases. Consensus clustering analysis was performed to identify novel molecular subgroups. Tumor immune status was assessed using estimating stromal and immune cells in malignancy using expression data, microenvironment cell populations, and single-sample gene set enrichment analysis analyses. Functional analysis, including gene ontology, gene set variation analysis, and gene set enrichment analysis, was conducted to explore potential mechanisms. A prognostic risk model was constructed using the LASSO algorithm and multivariate Cox regression analysis. Decision trees and nomograms were developed for survival prediction. SenMayo classified ccRCC patients into 2 molecular subtypes with significantly different survival rates, and significant differences in their immune status, characterized by poor prognosis with relatively high immune status. Besides, the differentially expressed genes between the 2 subgroups were mainly enriched in immune-related pathways. The burden of aging tissues and cells may lead to immune dysregulation and drug resistance, which could contribute to poor prognosis in ccRCC patients. Risk models, decision trees, and nomogram for ccRCC survival prediction have great potential applications. In conclusion, our study establishes a clear association between aging in ccRCC and the immune microenvironment, demonstrating the predictive potential of senescence genes for ccRCC prognosis.