Prognostic Value and Immune Relevance of Ultrafiltration Failure–Related Genes in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is a common malignancy characterized by intratumoral heterogeneity, affecting tumor progression and immune regulation. Although ultrafiltration (UF) failure has been clinically associated with kidney disease and ccRCC, the underlying molecular mechanisms remain poorly understood. Here, we developed a UF failure–related gene signature (UFFRGS) by integrating single-cell and bulk RNA sequencing data from TCGA-KIRC and E-MTAB-1980 cohorts. A total of 162 UF failure–related genes were identified, and 117 machine learning algorithm combinations were applied to construct a robust prognostic model comprising 37 key genes. UFFRGS stratified patients into high- and low-risk groups with significant survival differences. High-risk patients exhibited increased infiltration of CD8⁺ T cells, regulatory T cells, and activated CD4⁺ memory T cells, while low-risk patients showed enrichment of M2 macrophages and monocytes, reflecting immune heterogeneity. Mutation analysis revealed distinct patterns in VHL, PBRM1, and SETD2 between risk groups. Drug sensitivity analysis further indicated differential responses to multiple chemotherapeutic agents, providing potential guidance for individualized therapy. Among the core genes, CSNK1E was highlighted as a key prognostic factor, with high expression associated with poor survival and elevated in T4 tumors. GSVA suggested CSNK1E may promote tumor progression via Wnt/β-catenin and hormone-related pathways. In summary, UFFRGS is a stable, reliable prognostic tool that captures molecular and immune heterogeneity in ccRCC, offering insights for risk stratification and potential therapeutic intervention.