Abstract
BACKGROUND: Bladder urothelial carcinoma (BLCA) is a prevalent malignancy with high recurrence rates and limited therapeutic options, necessitating the identification of novel biomarkers for precision medicine. This study investigates the expression and clinical significance of multivesicular body subunit 12B (MVB12B) in BLCA, aiming to evaluate its potential as a prognostic biomarker and therapeutic target. METHODS: We systematically evaluated MVB12B expression across 33 cancer types from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets, and the expression of MVB12B in BLCA was verified using the GSE3167 dataset. Next, the expression of MVB12B in BLCA patients with different clinicopathologic features was analyzed. Then, survival analysis was conducted through the Encyclopedia of RNA Interactomes (ENCORI) database. The receiver operating characteristic (ROC) curves were conducted to assess the diagnostic values of MVB12B. Furthermore, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a protein-protein interaction (PPI) network, and gene set enrichment analysis (GSEA) was performed to explore potential pathways through which MVB12B might influence BLCA. Finally, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and cellular experiments were used to investigate the role of MVB12B in BLCA. RESULTS: Our study reported that MVB12B was significantly downregulated in 14 cancer types, particularly in BLCA, in which low expression correlated with advanced tumor stage (III & IV), histological grade (high), and worse overall survival in BLCA patients. PPI networks identified MVB12B's interactions with endosomal sorting complex required for transport (ESCRT) components, and GSEA revealed that MVB12B was significantly involved in keratinization and intermediate filament organization. Experimental validation in clinical samples and BLCA cell lines (T24, UM-UC-3) revealed that MVB12B expression was reduced in tumor tissues and BLCA cell lines. Functional assays demonstrated that MVB12B overexpression suppressed BLCA cell proliferation and migration in vitro, indicating its tumor-suppressive role. CONCLUSIONS: MVB12B functions as a tumor-suppressive role in BLCA and is associated with good prognosis in BLCA patients. MVB12B can be used as a potential biomarker for prognosis and therapeutic of BLCA.