MGMT promoter methylation status and MGMT and CD133 immunohistochemical expression as prognostic markers in glioblastoma patients treated with temozolomide plus radiotherapy.
MGMT promoter methylation status and MGMT and CD133 immunohistochemical expression as prognostic markers in glioblastoma patients treated with temozolomide plus radiotherapy.
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DOI：
10.1186/1479-5876-10-250
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发表时间：
2012-12-17
影响因子：
7.4
通讯作者：
Aránega A
中科院分区：
文献类型：
--
作者：
Melguizo C;Prados J;González B;Ortiz R;Concha A;Alvarez PJ;Madeddu R;Perazzoli G;Oliver JA;López R;Rodríguez-Serrano F;Aránega A
CD133抗原是胶质母细胞瘤(GBM)中耐放疗和耐化疗干细胞群的标志。O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)与替莫唑胺(TMZ)耐药有关。我们的建议是分析CD133抗原和启动子甲基化以及MGMT蛋白表达在接受放疗和TMZ治疗的同种GBM患者中的预后意义。并对这些GBM标记之间的可能联系进行了探讨。对78例接受放射治疗的GBM患者的MGMT和CD133进行分析。亚硫酸氢盐处理后，用甲基化特异性聚合酶链式反应检测MGMT基因启动子甲基化。用免疫组织化学自动定量系统检测MGMT和CD133的表达。根据Kaplan-Meier方法计算总生存率和无进展生存率。MGMT基因启动子甲基化34例(44.7%)，未甲基化42例(55.3%)。观察到MGMT启动子甲基化与患者生存显著相关。在未甲基化的肿瘤中，MGMT低表达占52.4%，高表达占47.6%。甲基化肿瘤中，MGMT低表达者占58.8%，高表达者占41.2%。未发现MGMT启动子甲基化与MGMT表达或MGMT表达与生存期的相关性。与最近的结果相比，CD133的表达不是GBM患者的预测标记物。CD133表达与MGMT蛋白表达或MGMT启动子甲基化的可能相关性分析均为阴性。我们的结果支持这样的假设，即MGMT启动子甲基化状态而不是MGMT表达可能是治疗GBM患者的预测生物标志物。此外，CD133不应用于评估这些患者的预后。未来的研究将是必要的，以确定其临床用途。
The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. Seventy-eight patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan–Meier method. The MGMT gene promoter was found to be methylated in 34 patients (44.7%) and unmethylated in 42 patients (55.3%). A significant correlation was observed between MGMT promoter methylation and patients’ survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative. Our results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these patients. Future studies will be necessary to determine its clinical utility.
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影响因子：
4.8
作者：
Cao, Van Thang;Lung, Tae-Young;Chae, Hong-Jae
通讯作者：
Chae, Hong-Jae
影响因子：
3.7
作者：
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Figarella-Branger, Dominique
DOI：
10.1016/j.ijrobp.2011.12.086
发表时间：
2012-11-01
影响因子：
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作者：
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通讯作者：
Suh, Chang-Ok
影响因子：
3.9
作者：
Minniti, Giuseppe;Salvati, M.;Giangaspero, F.
通讯作者：
Giangaspero, F.
影响因子：
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作者：
Nakasu, Satoshi;Fukami, Tadateru;Matsuda, Masayuki
通讯作者：
Matsuda, Masayuki