Unraveling the Prognostic Significance of BRCA1-Associated Protein 1 (BAP1) Expression in Advanced and Castrate-Resistant Prostate Cancer.

Abstract

Prostate cancer (PCa) is ranked as one of the top cancers affecting men in Western societies. BRCA1-associated protein 1 (BAP1) expression significance has been observed in various cancers, including prostate cancer. The search for prognostic models allowing better risk stratification and prediction of disease progression in prostate cancer patients is still of major clinical need. Our data showed that nuclear BAP1 expression is the most associated with cancer clinical outcomes and other biomarkers. The data confirmed that decreased BAP1 nuclear expression is linked to aggressive tumors and poorer prognosis. We assessed BAP1 expression in 202 cases, including advanced and castrate-resistant PCa (CRPCa). Our data indicated low BAP1 nuclear expression in advanced and castrate-resistant disease (CRPCa). Furthermore, there was a significant difference between high and low BAP1 nuclear expression relative to the patient's clinical outcome. In the present cohort, decreased BAP1 intensity exhibited a significant association with unfavorable overall survival (OS) (HR 2.31, CI: 1.38-3.86, p = 0.001) and cause-specific survival (CSS) (HR 2.44, CI: 1.24-4.78, p = 0.01). Additionally, this association was more pronounced when low BAP1 expression (high risk) was combined with other common PCa genomic alterations such as phosphatase and tensin homolog (PTEN) loss or ETS-related gene (ERG)-positive cases, resulting in higher unfavorable OS and CSS. Conversely, high BAP1 nuclear expression (moderate and high intensity) combined with no ERG expression or PTEN (moderate or high expression), p53 (wild type), and androgen receptor (AR) (low/moderate intensity) showed better association with higher survival rates. All these data support the notion that BAP1 functions as a tumor suppressor. Integrating BAP1 status with other genomic alterations offers a more comprehensive understanding of disease aggressiveness.