Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide
Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide
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DOI：
10.1007/s11060-010-0324-4
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发表时间：
2011-04-01
影响因子：
3.9
通讯作者：
Giangaspero, F.
中科院分区：
文献类型：
--
作者：
Minniti, Giuseppe;Salvati, M.;Giangaspero, F.
启动子甲基化对o -6-甲基鸟嘌呤- dna甲基转移酶（MGMT）基因的表观遗传沉默与接受烷基化剂治疗的新诊断的多形性胶质母细胞瘤（GBM）成年患者的无进展生存期（PFS）和总生存期（OS）的改善相关。本研究的目的是确定MGMT与放疗（RT）和替莫唑胺（TMZ）治疗的老年GBM患者的生存之间的相关性。本研究于2005年2月至2009年9月对83例经组织学证实的70岁及以上的GBM患者进行了RT + TMZ治疗。通过聚合酶链式反应分析确定MGMT启动子的甲基化状态。中位PFS和OS分别为7.5和12.8个月。42例（50.6%）患者MGMT启动子甲基化，41例（49.4%）患者未甲基化。甲基化患者的中位OS为15.3个月，未甲基化患者的中位OS为10.2个月（P = 0.0001）。甲基化肿瘤的中位PFS为10.5个月，非甲基化肿瘤的中位PFS为5.5个月（P = 0.0001）。在多变量分析中，MGMT甲基化状态成为OS和PFS最强的独立预后因素（P分别= 0.004和P = 0.005）。本研究结果提示MGMT甲基化状态可能是放疗和TMZ治疗老年GBM患者更好的OS和PFS的重要预后因素。
Epigenetic silencing of the O-6-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.