WDR72 as a Novel Prognosis-Predictive Biomarker Linked to Immune Infiltration and Poor Prognosis in Clear Cell Renal Cell Carcinoma

Background: Clear cell renal cell carcinoma (ccRCC) is a highly heterogeneous cancer type that lacks early diagnostic markers and effective targets for immunotherapy. WD repeat-containing protein 72 (WDR72) mutations have been linked to renal dysfunction and renal tubular acidosis. However, the potential prognosis-predictive value of WDR72 in ccRCC remains unelucidated. Methods: The current research used The Cancer Genome Atlas (TCGA) data to explore the expression and prognosis-predictive value of WDR72 in various solid tumors, including ccRCC. The analysis was validated using the TCGA–ccRCC cohort and Human Protein Atlas. The biological processes and signaling pathways linked to the expression of WDR72 were identified by conducting Gene Ontology and gene set enrichment analysis. Cox regression analysis was utilized to measure the prognosis-predictive value of WDR72 in ccRCC. Moreover, the association of WDR72 expression levels with immune cell infiltration, methylation, m6A, tumor mutation burden, immune checkpoint molecules, and drug sensitivity was analyzed. Finally, the study was verified by conducting quantitative real-time polymerase chain reaction and cytological experiments in ccRCC. Results: A pan-cancer analysis noted that low WDR72 expression levels were strongly linked to poor overall survival and progression-free interval in individuals with ccRCC. The WDR72 levels were remarkably reduced in ccRCC tissues in comparison with the adjacent tissues, and WDR72 was identified as an independent predictor of patients with ccRCC. Pathway enrichment analysis showed a close relationship between genes related to WDR72 and fat metabolism. Low WDR72 expression in ccRCC was linked to higher immune cell infiltration, stronger tumor mutation burden, and higher immune checkpoint molecules. Furthermore, individuals with ccRCC and low WDR72 expression had lower IC50 values for most drugs. Conclusion: Low WDR72 expression is strongly linked to the progression, prognosis, and microenvironmental immune regulation of individuals with ccRCC. Moreover, it may hold potential as a valuable prognostic biological marker and therapeutic measure for ccRCC. The findings provide a basis for future research by exploring the role of WDR72 in ccRCC tumor development.