Different prognostic roles of tumor suppressor gene BAP1 in cancer: A systematic review with meta-analysis

Genes Chromosomes Cancer. 2016 Oct;55(10):741-9. doi: 10.1002/gcc.22381. Epub 2016 Jul 7.

Abstract

Biallelic inactivation of the tumor suppressor gene BRCA1-associated protein 1 (BAP1) has been demonstrated in several cancers, but its prognostic role has not been completely explained. We aimed to investigate the risk associated with loss of BAP1 (BAP1-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS were searched from database inception until 09/15/2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of BAP1 (BAP1+) vs. BAP1- were included. Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to BAP1- adjusted for potential confounders. From 261 hits, 12 studies (including 13 cohorts) with 3,447 participants (BAP1-: n = 697; BAP1+: n = 2,750), with a median follow-up over 60 months, were meta-analyzed. Compared to BAP1+, BAP1- significantly increased all-cause mortality, cancer-specific mortality and risk of recurrence in all the tumor types analyzed, except for mesothelioma, in which the presence of BAP1 mutations correlates with a better prognosis. Furthermore, we demonstrated that BAP1 mutated colorectal and renal carcinomas are associated with high-tumor grading (P < 0.0001), and that BAP1 mutated is more common in women than in men (P < 0.0001). In conclusion, on the basis of our meta-analysis, we have demonstrated a peculiar role of BAP1 in influencing the prognosis in cancer. Thus, BAP1 could be considered as an important potential target for personalized medicine. © 2016 Wiley Periodicals, Inc.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • Mutation
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasms / genetics*
  • Neoplasms / mortality
  • Prognosis
  • PubMed
  • Risk Factors
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin Thiolesterase / genetics*

Substances

  • BAP1 protein, human
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase