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

## TL;DR

Low BAP1 expression in prostate cancer is linked to worse survival and more aggressive disease, suggesting it could help predict outcomes when combined with other genetic markers.

## Contribution

This study identifies BAP1 as a potential prognostic biomarker in advanced and castrate-resistant prostate cancer when combined with other genomic alterations.

## Key findings

- Lower BAP1 nuclear expression is significantly associated with worse overall and cause-specific survival in prostate cancer patients.
- BAP1 expression combined with PTEN loss or ERG positivity predicts more aggressive disease and poorer outcomes.
- High BAP1 expression correlates with better survival when paired with favorable genomic profiles like wild-type p53 and low AR expression.

## Abstract

Prostate cancer remains one of the major cancers affecting men worldwide. Currently, reliable biomarkers to associate with disease progression are in need. We assessed the expression significance between BAP1 and prostate cancer patients’ outcomes. The results showed that lower expression of BAP1 is associated with worse overall survival and lethal disease vs. those with higher intensity. BAP1 expression was also correlated with other known genomic changes in prostate cancer. Incorporating BAP1 expression may have prognostic value in men affected by prostate cancer.

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.