The Role Of BAP1 Expression And Clinical Significance In Oral Mucosal Melanoma

PURPOSEBAP1 is a novel tumor suppressor.It has been reported to be related to cutaneous and uveal melanoma.However,the relationship between BAP1 and oral mucosal melanoma remains unclear.The current study aims to investigate the rate of BAP1 mutation,the prognostic value of BAP1 protein expression and the possible tumorsuppressing mechanism of BAP1 in oral mucosal melanoma.METHODSTo investigate the rate of BAP1 mutation in oral mucosal melanoma,Sanger sequencing was performed in tumor tissue samples and blood samples of 12 patients.IHC assessment was performed in the tumor samples in order to reveal the relationship between BAP1 mutation and protein expression.IHC assessment of BAP1 protein expression was performed in samples of 62 patients with oral mucosal melanoma.The data of the patients was reviewed and retrived retrospectively.Cox proportional hazards model was performed to determine the influence of loss of BAP1 expression after controlling for other factors.The logistic regression was applied to evaluate odds ratios for distant metastasis.To investigate the possible tumor-suppressing mechanism of BAP1,BAP1 gene was silenced in oral mucosal melanoma cell line ME by small RNA interference.The mRNA expression of Nanog,Oct-4,Cyclin D1,Cyclin E1,HDAC1/2 was assessed by qPCR.RESULTSBAP1 mutation was detected in oral mucosal melanoma,and the rate of mutation was up to 33.3%.BAP1 mutation was significantly associated with loss of BAP1 protein expression in oral mucosal melanoma.Loss of BAP1 protein expression in tumor cells was associated with the overall survival of patients with oral mucosal melanoma.Loss of BAP1 expression was proved to be an independent predictive factor of poor prognosis.Meanwhile,BAP1 expression was associated with risk of distant metastasis.The mRNA expression of Nanog?Oct-4?Cyclin D1?Cyclin E1 and HDAC1/2 was up-regulated after BAP1 gene was silenced by siRNA in oral mucosal melanoma.CONCLUSIONSBAP1 gene is with a relatively high rate of mutation in oral mucosal melanoma.Loss of BAP1 protein expression is an independent prognostic factor of oral mucosal melanoma,and is associated with risk of distant metastasis.BAP1 gene probably associates with differentiation,cell cycle and HDAC expression in oral mucosal melanoma.