Epigenetic Alterations in Renal Clear Cell Carcinoma: A Comprehensive Expression and Clinical Outcome Analysis

Renal clear cell carcinoma (ccRCC) presents a unique landscape of genetic and epigenetic modifications, the understanding of which is crucial for the development of targeted therapies and improved prognostication. This study explores the differential expression of histone‐related genes (HRGs) in ccRCC and correlates these findings with patient clinical outcomes. By leveraging the Cancer Genome Atlas (TCGA) data, we performed a robust multidimensional analysis of HRG expression profiles in ccRCC versus adjacent normal tissues. Our results demonstrate a significant upregulation of several key epigenetic regulators, including UHRF1, KDM5A, EZH2, PRDM6, and TWIST1, in tumor samples, with statistical significance suggesting their involvement in tumorigenesis and progression. Paired expression analysis within patient‐matched samples confirmed the consistency of overexpression in tumors. The prognostic relevance of these genes was underscored through survival analyses, which revealed a clear stratification of patients into distinct risk categories based on their expression profiles. The integration of these genetic markers with clinical parameters facilitated the development of a predictive nomogram, yielding a quantifiable tool for survival prediction. Our comprehensive analysis elucidates the profound impact of epigenetic dysregulation in ccRCC and proposes a novel set of biomarkers for disease diagnosis, prognostic stratification, and potential therapeutic targeting, marking a significant stride toward precision oncology in renal cancer.