Pan-cancer analysis of the prognostic and immunological role of BRCA1-associated protein 1 gene (BAP1): Friend or foe?

Abstract

BackgroundBRCA1-associated protein 1 gene (BAP1) plays a key role in some cancers. However, it has not yet been elucidated whether BAP1 modulates the pathogenesis and progression of human cancers through some common cellular and molecular mechanisms, and a pan-cancer analysis for the roles of BAP1 has not yet been conducted. MethodsA systematic assessment of the BAP1 gene was presented using bioinformatics analysis and R software. Based on gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, differential expression of BAP1, survival prognosis and genetic alterations of BAP1, correlations between BAP1 expression and immune infiltrates, enrichment analysis and receiver operating curves (ROC) were performed across 33 TCGA cancers. ResultsBAP1 was highly expressed in several cancers and high BAP1 expression resulted in different survival prognoses. BAP1 DNA methylation status was changed in uveal melanoma (UVM) cases and a high level of BAP1 phosphorylation was found at the S292 locus in several cancers (colon cancer, lung adenocarcinoma, breast cancer, ovarian cancer, and uterine cancer). The statistically significant correlations of BAP1 expression and immune infiltration may contribute to the prognostic survivals in several cancers including UVM, skin cutaneous melanoma (SKCM), and lung adenocarcinoma (LUAD). Additionally, the correlations between BAP1 expression and tumor mutation burden (TMB)/microsatellite instability (MSI) across TCGA cancers were also explored. Finally, the analysis revealed that BAP1 expression level had high sensitivity and specificity for liver hepatocellular carcinoma (LIHC), kidney renal clear cell carcinoma (KIRC), and pancreatic adenocarcinoma (PAAD) patients. ConclusionThis study has revealed statistically significant correlations of BAP1 expression with survival analysis, DNA methylation, protein phosphorylation, genetic alteration, and immune infiltration across multiple TCGA cancers, suggesting that BAP1 may potentially serve as a potential therapeutic target and prognostic biomarker for several cancers.