Shen Dong, Liu Tao, Lin Qingfen, Lu Xiangdong, Wang Qiong, Lin Feng, Mao Weidong
Department of Oncology, the Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, P.R. China.
PLoS One. 2014 Sep 11;9(9):e107558. doi: 10.1371/journal.pone.0107558. eCollection 2014.
Promoter methylation of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene has been considered a prognostic marker and has become more important in the treatment of glioblastoma. However, reports on the correlation between MGMT and clinical outcomes in Chinese glioblastoma patients are very scarce. In this study, quantitative methylation data were obtained by the pyrosequencing of tumor tissues from 128 GBM patients. The median overall survival (OS) was 13.1 months, with a 1-year survival of 45.3%. The pyrosequencing data were reproducible based on archived samples yielding data for all glioblastomas. MGMT promoter methylation was detected in 75/128 cases (58.6%), whereas 53/128 (41.4%) cases were unmethylated. Further survival analysis also revealed that methylation was an independent prognostic factor associated with prolonged OS but not with progression-free survival (PFS) (p = 0.029 and p = 0.112, respectively); the hazard radios were 0.63 (95% CI: 0.42-0.96) and 0.72 (95% CI: 0.48-1.09), respectively. These data indicated that MGMT methylation has prognostic significance in patients with newly diagnosed high-grade glioblastoma undergoing alkylating agent-based chemotherapy after surgical resection.
O(6)-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因的启动子甲基化被认为是一种预后标志物,在胶质母细胞瘤的治疗中变得越来越重要。然而,关于中国胶质母细胞瘤患者中MGMT与临床结局之间相关性的报道非常稀少。在本研究中,通过对128例胶质母细胞瘤患者的肿瘤组织进行焦磷酸测序获得了定量甲基化数据。中位总生存期(OS)为13.1个月,1年生存率为45.3%。基于存档样本产生的所有胶质母细胞瘤数据,焦磷酸测序数据具有可重复性。在128例病例中有75例(58.6%)检测到MGMT启动子甲基化,而128例中有53例(41.4%)未甲基化。进一步的生存分析还显示,甲基化是与OS延长相关的独立预后因素,但与无进展生存期(PFS)无关(分别为p = 0.029和p = 0.112);风险比分别为0.63(95%CI:0.42 - 0.96)和0.72(95%CI:0.48 - 1.09)。这些数据表明,MGMT甲基化在接受手术切除后基于烷化剂化疗的新诊断高级别胶质母细胞瘤患者中具有预后意义。