Multi-omic analysis reveals elevated BRI3BP expression associated with hepatocellular carcinoma progression and poor prognosis

BRI3BP, an RNA-binding protein upregulated in multiple cancers, plays an undefined role in hepatocellular carcinoma (HCC). This study investigates its diagnostic and prognostic potential in HCC. Multi-omics analysis of TCGA and GEO data identified BRI3BP-interacting genes and enriched pathways. Genomic and epigenetic alterations were assessed using cBioPortal and MethSurv. Immune infiltration was profiled via ssGSEA and TIMER 2.0. Prognostic relevance was validated through survival analysis, Cox regression, and experimental assays. BRI3BP was overexpressed in HCC and correlated with advanced tumor stage, shorter overall survival (OS), and disease-free survival (DFS). Functional enrichment linked BRI3BP to cell cycle regulation, Rho GTPase activity, and copper homeostasis. Analysis of transcriptomic data revealed that BRI3BP expression also significantly correlated with immune cell infiltration and an immunosuppressive microenvironment, validated by immunohistochemistry showing reduced CD8 + and increased CD68 + cells in high-BRI3BP samples. In vitro, BRI3BP overexpression promoted HCC cell migration and invasion and activated the ROCK signaling pathway, suggesting potential involvement in tumor progression. Drug sensitivity assays confirmed lower lapatinib IC50 in overexpression models. High BRI3BP expression correlates with aggressive HCC phenotypes, poorer survival, and dysregulated oncogenic pathways, supporting its role as a prognostic biomarker and candidate therapeutic target.