The Prognostic Significance of BRCA1-Associated Protein 1(BAP1) in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Our plain-English summary of The Prognostic Significance of BRCA1-Associated Protein 1(BAP1) in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis, by J. Hong, X. Dai, J. Yuan, et al (Clinical Medicine Insights. Oncology, 2026).

The study

• Authors: J. Hong, X. Dai, J. Yuan, C. Chen, Z. Huo, C. Xu, Q. Wang
• Journal: Clinical Medicine Insights. Oncology
• Published: 2026;20:11795549261472695
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) originates from pleural mesothelial cells and represents a highly aggressive malignancy. Characterized by a prolonged latency period, poor survival prognosis, and non-specific clinical manifestations, MPM poses significant diagnostic and therapeutic challenges. BRCA-1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme involved in chromatin regulation, homologous recombination, and programmed cell death. Although multiple studies have suggested that BAP1 loss or mutation holds prognostic significance in malignant pleural mesothelioma, this remains a matter of debate.

Methods: A meta-analysis was conducted using data from the Web of Science, PubMed, Embase, Cochrane, and CNKI up to October 21, 2025. We included studies involving patients with malignant pleural mesothelioma that assessed the prognostic significance of BAP1. These studies reported hazard ratios (HR) and 95% confidence intervals (CI) for median overall survival (mOS) and median progression-free survival (mPFS).

Results: A total of 14 articles meeting the inclusion criteria were identified, encompassing 1,835 patients. We conducted both univariate and multivariate analyses of mOS, revealing that BAP1 deletion or mutation consistently correlated with improved prognosis, with hazard ratios of 0.51 (95% CI, 0.45-0.58, P < 0.0001) and 0.62 (95% CI, 0.54-0.71, P < 0.0001), respectively. The values were statistically significant (P < 0.0001). Furthermore, analyses of mPFS continued to demonstrate that BAP1 deletion or mutation consistently correlated with improved prognosis (U: HR = 0.62, 95% CI = 0.39-0.99, P = 0.04; M: HR = 0.79, 95% CI = 0.51-1.24, P = 0.31), though this did not reach statistical significance. Sensitivity analyses confirmed the robustness of these findings, with minimal heterogeneity between studies.

Conclusion: BAP1 serves as a potential prognostic marker for MPM, with its deletion or mutation indicating a favourable prognosis for patients. However, whether it provides valuable insights for various treatment strategies, including immunotherapy, requires further clinical investigation to determine.

© The Author(s) 2026.

In plain English

This was a systematic review and meta-analysis of earlier published studies. The authors searched five databases up to 21 October 2025 for studies of malignant pleural mesothelioma that compared survival in patients whose tumours had BAP1 deletion or mutation with patients whose tumours kept BAP1. Fourteen articles covering 1,835 patients were included. In the pooled unadjusted (univariate) analysis, patients with BAP1 deletion or mutation had a lower hazard of death: hazard ratio 0.51 (95% CI 0.45-0.58). The adjusted (multivariate) result was printed as 0.66 (95% CI 0.59-0.77) in the results but as 0.62 in the abstract. For progression-free survival, hazard ratios were 0.62 (95% CI 0.39-0.99, P=0.04) unadjusted and 0.79 (95% CI 0.51-1.24, P=0.31) adjusted. The authors said these did not reach statistical significance. BAP1 loss was most common in epithelioid tumours (66.7%), a subtype with a better prognosis, and the authors noted this could confound the finding. The authors concluded that BAP1 is a potential prognostic marker for overall survival. Asbestos exposure was not analysed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review and meta-analysis of observational cohort studies (prospective and retrospective), pooling hazard ratios with a random-effects model
• Who was studied: 14 published studies totalling 1,835 patients with malignant pleural mesothelioma, from Turkey, Australia, Denmark, Italy, Israel, the United States, Egypt and Austria. Study sizes ranged from 17 to 369 patients. Literature was searched up to 21 October 2025.
• Exposure: Tumour BAP1 status: BAP1 deletion or mutation compared with BAP1 retained ('positive' or 'preserved'). Status was assessed mostly by immunohistochemistry, and in some studies by sequencing or other molecular methods. Asbestos exposure was not analysed.
• Main results:
  • Pooled univariate analysis of overall survival: patients with BAP1 deletion or mutation had longer survival than BAP1-positive patients, HR 0.51 (95% CI 0.45-0.58, P < 0.0001).
  • Pooled multivariate analysis of overall survival: HR 0.66 (95% CI 0.59-0.77, P < 0.0001) for BAP1 deletion or mutation compared with BAP1-positive patients. The abstract instead gives 0.62 (95% CI 0.54-0.71).
  • Progression-free survival: univariate HR 0.62 (95% CI 0.39-0.99, P=0.04) and multivariate HR 0.79 (95% CI 0.51-1.24, P=0.31). The authors described these as not reaching statistical significance.
  • In ten studies with 1,157 pathologically confirmed patients, 626 (approximately 54%) had BAP1 deletion or mutation.
  • In nine studies with 1,039 patients, BAP1 deletion or mutation was found in 66.7% of epithelioid, 51.2% of biphasic and 20.1% of sarcomatoid tumours.
  • Egger and Begg tests showed no significant publication bias. After trim-and-fill adjustment, the univariate overall survival HR was 0.63 (95% CI 0.54-0.73), still statistically significant.
  • Excluding the one study that used only next-generation sequencing left the univariate overall survival HR at 0.51 (95% CI 0.45-0.58) across the remaining seven studies.
  • Subgroup analysis by histological subtype could not be done properly, because only two studies examined BAP1 within subtypes and neither gave specific values.
• The authors' conclusion: The authors concluded that BAP1 is a potential prognostic marker for malignant pleural mesothelioma, predicting overall survival with statistical significance. They said progression-free survival data were largely unavailable, and that any value for guiding treatment, including immunotherapy, needs further clinical study.
• Limitations the authors state:
  • Relatively few studies were included, and most were retrospective.
  • Limited geographical diversity, with most studies from Italy and Australia.
  • Non-English studies were excluded, and unpublished negative results may be missing.
  • Mixing univariate and multivariate hazard ratios may add heterogeneity, because studies adjusted for different confounders.
  • BAP1 loss is more common in epithelioid mesothelioma, which itself has a better prognosis, so the survival benefit may be confounded.
  • Few studies and small samples reported progression-free survival.
  • Disease-free and disease-specific survival could not be analysed.
  • BAP1 immunohistochemistry results may vary between observers and with technical factors.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Pleural Mesothelioma, Systematic Review, Meta-Analysis, Mesothelial Cells, Latency, Prognosis, Hazard Ratio.

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