Clinical correlation of MGMT protein expression and promoter methylation in Chinese glioblastoma patients

Abstract

Promoter methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene has been considered as a prognostic maker and increasingly emphasized in the treatment of glioblastoma multiforme (GBM). Contrastingly, the correlation of MGMT with clinical outcomes in Chinese glioblastoma patients has not been elucidated systematically. In the present study, tumor tissues from 172 GBM patients were analyzed for MGMT protein expression by immunohistochemistry. Of these, 79 were also subjected to pyrosequencing for MGMT promoter methylation analysis. MGMT protein overexpression was found in 109/172 (63.4%) GBM samples. And no significant survival difference was observed between the patients with MGMT overexpression and low expression in terms of progression-free survival or overall survival (P = 0.605 and P = 0.565, respectively). Meanwhile, MGMT promoter methylation was detected in 26/79 cases (32.9%), whereas 53/79 (67.1%) samples were unmethylated. Further survival analysis also revealed that MGMT promoter methylation status cannot predict patients progression-free survival and overall survival (P = 0.906 and P = 0.548, respectively). The integrated analysis showed that there was significant negative correlation between MGMT protein expression and promoter methylation (P = 0.004). These results underscore that, in Chinese GBM patients, (a) MGMT protein expression level was not a prognostic factor, (b) overall survival but not progression-free survival showed a trend toward increase in patients with MGMT promoter methylation, although the difference was not significant statistically and this observation has to be validated in larger patients cohort, (c) there was a significant correlation between MGMT protein expression in immunohistochemistry and MGMT promoter methylation by pyrosequencing.