Pan‐Cancer Analysis Identifies DIP2B as a Potential Biomarker That Inhibits Kidney Renal Clear Cell Carcinoma Progression

ABSTRACT Disco interacting protein 2 homolog B (DIP2B) is a protein‐coding gene implicated in various biological processes, including embryonic development, cell cycle regulation, DNA repair, and transcriptional regulation. While its precise role in cancer remains largely unknown, emerging evidence suggests its potential involvement in tumorigenesis. In this study, we provide a comprehensive analysis of DIP2B in cancer, exploring its expression patterns, molecular functions, and potential clinical implications across different cancer types. We examined the expression, dysregulation, and prognostic significance of DIP2B. The mRNA and protein expression status of DIP2B was determined using data from TCGA, GTEx, and UALCAN. Using TCGA database data, we investigated associations between DIP2B expression and gene mutations, survival outcomes, DNA methylation, immune cell infiltration, tumor mutation burden (TMB), and drug sensitivity. High DIP2B expression was associated with poor overall survival (OS) in BRCA, KICH, LUAD, MESO, SARC, and THCA, but with improved OS in KIRC. For disease‐specific survival (DSS), elevated DIP2B levels correlated with adverse outcomes in ACC, MESO, and UVM. GO and KEGG analyses implicated DIP2B in cytoskeleton organization, MAPK signaling, and ubiquitin‐dependent protein catabolism. Experimental validation in KIRC cells showed that DIP2B knockdown significantly reduced cell proliferation and migration. Conversely, DIP2B exhibited oncogenic functions in LUAD cells. These findings suggest DIP2B may serve as a potential prognostic and diagnostic biomarker, displaying a unique tumor‐suppressive role in KIRC progression.