Pan-cancer analysis identifies DIP2C as a favorable prognostic biomarker and suppressor of cell migration in kidney renal clear cell carcinoma

<title>Abstract</title> <p>Kidney renal clear cell carcinoma (KIRC) remains a major clinical challenge because of its molecular heterogeneity, variable treatment response, and limited prognostic precision using conventional clinicopathological indicators alone. DIP2C is a conserved member of the DIP2 family, but its cancer-related functions and clinical relevance remain incompletely defined. In this study, we performed a comprehensive pan-cancer analysis of DIP2C using TCGA, GTEx, HPA, CPTAC, cBioPortal, GEPIA2, TIMER, xCell, GDSC, CTRP, and related public datasets, followed by KIRC-focused prognostic modeling and in vitro functional validation. DIP2C expression showed cancer type-specific dysregulation and was downregulated in several tumor types, including KIRC. Survival analyses indicated that low DIP2C expression was associated with unfavorable outcomes in KIRC, and Cox regression analyses supported high DIP2C expression as an independent favorable prognostic factor for overall survival, disease-specific survival, and progression-free interval. DIP2C expression was also associated with DNA methylation, immune-cell infiltration, immune checkpoint genes, tumor mutational burden, microsatellite instability, coexpression networks, pathway enrichment, and anticancer drug sensitivity. Functional assays further demonstrated that siRNA-mediated DIP2C knockdown in 786-O and Caki-1 cells enhanced migratory behavior. These findings suggest that DIP2C may act as a context-dependent cancer regulator and a favorable prognostic biomarker with tumor-suppressive relevance in KIRC.</p>