title: Cytoplasmic expression of BAP1 as an independent prognostic biomarker for patients with gliomas.
abstract: BACKGROUND
  BRCA1-associated protein-1 (BAP1) has been investigated the prognostic value for some carcinomas, including mammary carcinoma, pulmonary carcinoma and mesothelioma and so on. However, the status of BAP1 expression and the relationship of that with overall survival were not still estimated in patients with gliomas. Therefore, it was necessary to investigate the effect of BAP1 expression for the survival of patients with gliomas in this study.
  
  
  METHODS
  Clinicopathological information of 229 patients with gliomas was used to perform the further analysis. We defined the nucleus expression of BAP1 score of median 0 and cytoplasmic expression of BAP1 score of median 100 as the rational cutoff value for survival analysis, respectively. These patients were categorized into the low cytoplasmic expression of BAP1 and the high expression of BAP1 group, presence of nucleus expression and absence of nucleus expression according to the corresponding cutoff point, respectively. The associations of clinicopathological characteristics with overall survival (OS) were investigated by univariate analysis in patients with gliomas. Multivariate analysis was further performed to find the independent prognostic indicator of OS by Cox regression model.
  
  
  RESULTS
  Thirty-nine of 229 patients (17.0%) with gliomas had the nucleus expression of BAP1, 213 of 229 patients (93.0%) had the cytoplasmic expression of BAP1, and 28 patients (12.2%) with both cytoplasmic and nucleus expression, 5 cases (2.2%) without neither cytoplasmic nor nucleus expression. Univariate analysis demonstrated that high cytoplasmic expression of BAP1, tumor location, tumor relapse, advanced clinical stage were significant linkage with worse OS (P<0.05). Multivariate analysis revealed that high cytoplasmic expression of BAP1 was a significantly independent biomarker for adverse OS (hazard ratio: 1.516, 95% CI: 1.029-2.234, P=0.035). In stratified analysis, we found that the patients with high cytoplasmic expression of BAP1 had the shorter overall survival than these with low cytoplasmic expression of BAP1 in the 190 patients without nucleus expression of BAP1 (P=0.001). ROC curve analysis showed that cytoplasmic expression of BAP1 was superior to nucleus expression of BAP1 as a predictive factor in patients with gliomas (AUC=0.583, P=0.030 vs. AUC=0.516, P=0.679).
  
  
  CONCLUSIONS
  This study suggested that cytoplasmic expression of BAP1 might be served as a valuable predictive biomarker of the prognosis in gliomas. High cytoplasmic expression of BAP1 might be benefit to identify patients who need to carry out further therapy.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Xin-Ke
authors.initials: XK
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Neurosurgery, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Sai
authors.affiliation: Department of Pediatric Surgery, The First Affiliated Hospital, Sun Yat-Sen University Guangzhou, China.
authors.forename: Hua-Dong
authors.initials: HD
authors.lastname: Chen
authors.affiliation: Department of Pediatric Surgery, The First Affiliated Hospital, Sun Yat-Sen University Guangzhou, China.
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Qiu-Liang
authors.initials: QL
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D003593:Cytoplasm / Q000737:chemistry*; D005260:Female; D005910:Glioma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D043222:Ubiquitin Thiolesterase / Q000032:analysis*
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; OS; ROC; cytoplasmic; gliomas; prognosis