Multi-omics pan-cancer analysis reveals an immunological role and prognostic potential of WDR76

Objectives WD repeat domain 76 (WDR76) significantly influences various metabolic and genomic processes, including RAS protein degradation, which plays a role in tumor cells. However, a systematic pan-cancer analysis of WDR76 has not been conducted. Therefore, this study aimed to identify the role of WDR76 in human tumors. Methods This study used publicly available databases and tools, including TCGA, UALCAN, GEPIA2, TIMER2.0, KMplotter, cBioPortal, STRING, Cytoscape, and TCGAplot, to investigate the potential roles of WDR76 in different types of tumors. Results WDR76 expression was higher in several tumor types; however, the prognostic associations varied by cancer and attenuated after covariate adjustment and FDR correction. Notably, promoter methylation of WDR76 was higher in tumors than in normal cells in multiple cancers. Deep deletions and point mutations were the most frequent alterations, with an overall frequency of approximately 1% in TCGA. Immune infiltration analysis using different algorithms revealed a correlation between CAF infiltration and different tumors, especially KIRC, KIRP, and LGG, with significant clinical outcomes. In the tumor immune microenvironment, WDR76 was positively correlated with different immune cells, stromal cells, immune checkpoint inhibitors, and stimulator-associated genes, suggesting a broad interaction with cancer immunity. The correlation between WDR76 and TMB and MSI was significant in UCEC, STAD, KIRC, and COAD. Functional and pathway enrichment analyses revealed an association between WDR76 and various cellular processes and functions. Conclusion Our analysis offers insights into WDR76’s context-dependent role, consistent with prior evidence of RAS degradation (tumor-suppressive), along with tumor-type-specific associations, prognostic significance, and immunological role across all tumors.