Integrated bioinformatics and experimental validation identify aging-related prognostic genes in clear cell renal...

Clear cell renal cell carcinoma (ccRCC) is the most common renal carcinoma subtype. Aging-related genes (ARGs) are implicated in ccRCC progression, though their mechanisms remain unclear. This study aimed to elucidate the molecular mechanisms of ARGs in ccRCC and identify potential prognostic biomarkers and therapeutic targets. Transcriptomic data from the cancer genome atlas (TCGA-ccRCC) cohort were analyzed. differentially expressed genes and ARGs were intersected to identify candidate genes. Prognostic ARGs were then screened using machine learning algorithms. A risk model was constructed and validated through survival analysis, stratifying patients into high- and low-risk groups. Functional enrichment, immune infiltration, and drug prediction analyses were performed. The expression levels of prognostic genes in ccRCC tissues were validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR). A total of 2312 differentially expressed genes and 307 ARGs were identified, of which 25 overlapping genes were selected as candidates. Seven ARGs were significantly associated with patient prognosis: protective PCK1, and risk-related TOP2A, TFAP2A, CCNA2, FOXM1, CDKN2A, and PLAU. High-risk patients showed reduced overall survival rates. Immune infiltration and checkpoint expression differed significantly between risk groups. decision curve analysis indicated high clinical utility. Drug prediction identified 69 potential therapeutic compounds, including tyrosine kinase and mTOR inhibitors. RT-qPCR validated 5 genes' expression, consistent with bioinformatics predictions, though discrepancies were observed in the expression patterns of FOXM1 and CDKN2A. Seven ARGs were identified as key prognostic markers in ccRCC. A robust risk model was established, providing insights into ARG-related mechanisms and potential diagnostic and therapeutic strategies.