Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili 100050, Dongcheng District, Beijing, China.
Med Oncol. 2012 Jun;29(2):1292-6. doi: 10.1007/s12032-011-9901-4. Epub 2011 Mar 11.
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.
O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）基因启动子甲基化已被认为是一种预后标志物，并在多形性胶质母细胞瘤（GBM）的治疗中得到越来越多的重视。然而，MGMT 与中国胶质母细胞瘤患者临床结局的相关性尚未得到系统阐明。在本研究中，通过免疫组织化学法分析了 172 例 GBM 患者的肿瘤组织中 MGMT 蛋白的表达情况。其中，79 例还进行了焦磷酸测序以分析 MGMT 启动子甲基化情况。在 172 例 GBM 样本中，发现 109 例（63.4%）存在 MGMT 蛋白过表达。MGMT 蛋白过表达组与低表达组在无进展生存期和总生存期方面均无显著生存差异（P = 0.605 和 P = 0.565）。同时，在 26 例病例中检测到 MGMT 启动子甲基化（32.9%），而 53 例病例（67.1%）为非甲基化。进一步的生存分析也表明，MGMT 启动子甲基化状态不能预测患者的无进展生存期和总生存期（P = 0.906 和 P = 0.548）。综合分析显示，MGMT 蛋白表达与启动子甲基化之间存在显著负相关（P = 0.004）。这些结果表明，在中国 GBM 患者中，（a）MGMT 蛋白表达水平不是预后因素，（b）尽管总体生存但无进展生存期显示出 MGMT 启动子甲基化患者增加的趋势，但统计学上差异无显著性，这一观察结果需要在更大的患者队列中进行验证，（c）免疫组化中 MGMT 蛋白表达与焦磷酸测序的 MGMT 启动子甲基化之间存在显著相关性。
