Objective  To systematically analyze the expression profile, prognostic value, genomic characteristics, biological functions, and associations with the immune microenvironment and therapeutic sensitivity of mitochondrial calcium uniporter dominant negative subunit beta (MCUB) across pan-cancer.

Methods  Based on public databases including TCGA, HPA, CancerSEA, STRING, GeneMANIA, the MCUB's mRNA and protein expression levels, genomic variations such as mutations and copy number variations (CNVs), prognostic correlations such as overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), progression-free survival (PFS), functional enrichment, protein interaction networks, immune infiltration features, and drug sensitivity in multiple tumors were comprehensively analyzed.

Results  High MCUB expression was significantly associated with poor prognosis in various cancers. Interaction network analysis revealed that MCUB interacted with proteins including the mitochondrial calcium uniporter (MCU) and histone methyltransferase (SETDB1), suggesting its potential involvement in tumor progression through regulating calcium signaling and epigenetic modifications. The correlation between MCUB expression and T-cell infiltration, along with its impact on prognosis, indicated its potential as a prognostic tumor biomarker and possible influence on the tumor immune microenvironment. Furthermore, drug sensitivity analysis revealed significant associations between MCUB expression levels and the efficacy of specific drugs, providing clues for developing therapeutic strategies targeting MCUB or its related pathways.

Conclusion  MCUB is highly expressed in multiple tumors and serves as an independent predictor of poor prognosis for patients with cancers such as clear cell renal cell carcinoma (KIRC) and lower-grade glioma (LGG). It promotes tumor progression by interacting with MCU and SETDB1 and influencing T-cell infiltration. The significant correlation between MCUB expression and drug sensitivity highlights its potential as a pan-cancer prognostic biomarker and therapeutic target for tumors like KIRC.

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