Prognostic and Clinicopathological Significance of BAP1 Protein Expression in Different Types of Cancer-A Meta-Analysis

Our plain-English summary of Prognostic and Clinicopathological Significance of BAP1 Protein Expression in Different Types of Cancer-A Meta-Analysis, by Z. Wang, X.Y. Wang, J. Li, et al (Genetic Testing and Molecular Biomarkers, 2018).

The study

• Authors: Z. Wang, X.Y. Wang, J. Li, W.W. Zhu
• Journal: Genetic Testing and Molecular Biomarkers
• Published: 2018;22(2):115-126
• Type of article: Meta-analysis
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background And Aims: The prognostic value of BRCA1-associated protein 1 (BAP1) expression in different cancer types remains controversial. The aim of this study was to identify the prognostic and clinicopathological significance of BAP1 gene expression.

Materials And Methods: The PubMed, Web of Science, and Embase databases were searched comprehensively for relevant studies. The pooled effects were calculated to investigate the association of BAP1 expression with cancer prognosis and clinicopathological features. The χ2 and I2 tests were performed to evaluate heterogeneity among the enrolled articles. If the p > 0.05 and I2 < 50%, a fixed-effects model was applied; and if the p < 0.05 and I2 > 50%, we used a random-effects model.

Results: A total of 26 studies covering 8043 patients were included in the meta-analysis. The correlation between BAP1 expression and patient survival was evaluated for 10 different cancer types. The pooled hazard ratio (HR) of BAP1 expression and overall survival (OS) was 0.83 (95% confidence interval [CI]: 0.61-1.12) with heterogeneity (I2 = 85.8%, p < 0.001), which indicated that the expression of BAP1 had no obvious impact on patient survival in the all-cancer cohort. However, subgroup analyses indicated that cancer type, rather than other parameters (geographic region, detection method, sample size, or comparison method), lead to this heterogeneity. BAP1 expression was a favorable predicative factor for OS in clear cell renal cell carcinoma (HR = 0.57, 95% CI: 0.47-0.69), non-small cell lung cancer (HR = 0.55, 95% CI: 0.32-0.96), and uveal melanoma (HR = 0.41, 95% CI: 0.27-0.62), while high expression of BAP1 was associated with poorer outcome in malignant pleural mesothelioma (HR = 2.03, 95% CI: 1.67-2.47).

Conclusion: Our study revealed that BAP1 expression tends to have different prognostic values in different cancer types. Clinically, BAP1 may serve as a promising marker for prognostic prediction for certain cancer types.

In plain English

This was a meta-analysis: the authors pooled results from earlier studies to ask whether the amount of a protein called BAP1 in tumor tissue is linked with how long cancer patients survive. It did not look at asbestos exposure. It included 26 studies covering 8043 patients with 10 different cancer types. Across all cancers combined, the pooled hazard ratio for overall survival was 0.83 (95% confidence interval 0.61 to 1.12). The authors read this as BAP1 having no obvious impact on survival overall. Results varied widely between studies, and the authors traced this mainly to cancer type. Higher BAP1 expression went with better overall survival in clear cell renal cell carcinoma, non-small cell lung cancer and uveal melanoma. In the group the authors labeled malignant pleural mesothelioma, it went with poorer outcome (hazard ratio 2.03, 95% confidence interval 1.67 to 2.47), though that group included one study of peritoneal mesothelioma. The authors concluded that BAP1 has different prognostic values in different cancer types. They noted that most studies were recent and that cohort studies are hard to control for confounders.

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: Meta-analysis (pooled analysis) of studies on BAP1 protein expression and cancer survival, found by searching PubMed, Web of Science and Embase
• Who was studied: 26 studies covering 8043 patients with 10 different cancer types, including breast, cholangiocarcinoma, clear cell renal cell carcinoma, colorectal, esophageal, gastric, glioma, malignant pleural mesothelioma, non-small cell lung cancer and uveal melanoma
• Exposure: Not asbestos. The factor studied was BAP1 protein (or gene) expression measured in tumor tissue, by immunohistochemistry, reverse phase protein arrays, quantitative real-time PCR or microarray
• Main results:
  • All cancers combined: the pooled hazard ratio for BAP1 expression and overall survival was 0.83 (95% CI 0.61 to 1.12), with high heterogeneity between studies (I2 = 85.8%, p less than 0.001)
  • The authors concluded that cancer type was the key reason for the differences between studies
  • Subgroup the authors label malignant pleural mesothelioma (six studies, one of which, Singhi et al. 2016 with 86 patients, is titled as a study of malignant peritoneal mesothelioma): high BAP1 expression was associated with poorer outcome (HR 2.03, 95% CI 1.67 to 2.47)
  • Clear cell renal cell carcinoma: patients with BAP1 loss had poorer prognosis (HR 0.57, 95% CI 0.47 to 0.69)
  • Non-small cell lung cancer: BAP1 expression was a favorable factor for overall survival (HR 0.55, 95% CI 0.32 to 0.96)
  • Uveal melanoma: BAP1 loss was a poor predictive factor for prognosis (HR 0.41, 95% CI 0.27 to 0.62)
  • Cholangiocarcinoma: no significant association between BAP1 expression and overall survival (HR 1.09, 95% CI 0.70 to 1.71)
  • Disease-free survival (11 articles, all cancers): high BAP1 expression was a favorable prognostic factor (HR 0.53, 95% CI 0.41 to 0.70)
  • Clear cell renal cell carcinoma: BAP1 expression was associated with lower frequency of tumor necrosis (OR 0.25, 95% CI 0.15 to 0.40)
  • Uveal melanoma: BAP1 expression was associated with a lower rate of ciliary body involvement (OR 0.16, 95% CI 0.05 to 0.49)
  • No significant publication bias was found for overall survival (Egger's test p = 0.972)
• The authors' conclusion: The authors concluded that BAP1 expression tends to have different prognostic values in different cancer types, and that it may be a promising prognostic predictor and potential therapeutic target in BAP1-associated cancers
• Limitations the authors state:
  • The studies on BAP1 and prognosis were published mainly in the previous 5 years, so further validation is needed
  • Cohort studies are difficult to control for confounders, which could affect the true impact of BAP1 on survival
  • Whether BAP1 is located in the cell nucleus or the cytoplasm may mean it works differently, and this was not resolved

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Meta-Analysis, Prognosis, Hazard Ratio, Overall Survival, confidence interval, Carcinoma, Non-Small Cell Lung Cancer.

Related studies

• Different prognostic roles of tumor suppressor gene BAP1 in cancer: A systematic review with meta-analysis — C. Luchini, N. Veronese, et al. (2016)
• The prognostic significance of BAP1, NF2, and CDKN2A in malignant peritoneal mesothelioma — A.D. Singhi, A.M. Krasinskas, et al. (2016)
• BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas — N. Leblay, F. Leprêtre, et al. (2017)
• Functional differences between wild-type and mutant-type BRCA1-associated protein 1 tumor suppressor against malignant mesothelioma cells — S. Hakiri, H. Osada, et al. (2015)
• Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions — I. Cozzi, F.A. Oprescu, et al. (2018)
• Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer — D. Owen, B.S. Sheffield, et al. (2017)

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