PURPOSE Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation and EGFR amplification are markers that may play a role in prognostication, treatment, and/or clinical trial eligibility. Quantification of MGMT and EGFR protein expression may offer an alternative strategy towards understanding GBM. Here, we quantify baseline expression of MGMT and EGFR protein in newly diagnosed GBM samples using mass spectrometry. We correlate findings with MGMT methylation and EGFR amplification statuses and survival. METHODS We retrospectively identified adult patients with newly diagnosed resected GBM. MGMT and EGFR protein expression were quantified using a selected reaction monitoring mass spectrometry assay. Protein levels were correlated with MGMT methylation and EGFR amplification and survival data. RESULTS We found a statistically significant association between MGMT protein expression and promoter methylation status (p = 0.02) as well as between EGFR protein expression and EGFR amplification (p < 0.0001). EGFR protein expression and amplification were more tightly associated than MGMT protein expression and methylation. Only MGMT promoter methylation was statistically significantly associated with progression-free and overall survival. CONCLUSIONS Unlike EGFR protein expression and EGFR amplification which are strongly associated, only a weak association was seen between MGMT protein expression and promoter methylation. Quantification of MGMT protein expression was inferior to MGMT methylation for prognostication in GBM. Discordance was observed between EGFR amplification and EGFR protein expression; additional study is warranted to determine whether EGFR protein expression is a better biomarker than EGFR amplification for clinical decisions and trial enrollment.

中文翻译：

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胶质母细胞瘤中MGMT和EGFR蛋白表达的特征及其与存活率的关系。

目的在成针对性的治疗时代，了解胶质母细胞瘤（GBM）的分子格局变得越来越重要。O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化和EGFR扩增是可能在预后，治疗和/或临床试验资格中起作用的标志物。MGMT和EGFR蛋白表达的定量分析可能为理解GBM提供了另一种策略。在这里，我们使用质谱法对新诊断的GBM样品中MGMT和EGFR蛋白的基线表达进行定量。我们将发现与MGMT甲基化和EGFR扩增状态及生存率相关联。方法我们回顾性鉴定了新诊断为切除的GBM的成年患者。使用选定的反应监测质谱分析法对MGMT和EGFR蛋白的表达进行定量。蛋白水平与MGMT甲基化和EGFR扩增以及生存数据相关。结果我们发现MGMT蛋白表达与启动子甲基化状态（p = 0.02）之间以及EGFR蛋白表达与EGFR扩增之间（p <0.0001）在统计学上具有显着相关性。EGFR蛋白的表达和扩增比MGMT蛋白的表达和甲基化紧密相关。在统计学上，只有MGMT启动子甲基化与无进展生存期和总生存期显着相关。结论与强相关的EGFR蛋白表达和EGFR扩增不同，MGMT蛋白表达与启动子甲基化之间仅存在弱关联。在GBM中，MGMT蛋白表达的定量低于MGMT甲基化。在EGFR扩增和EGFR蛋白表达之间观察到不一致。在临床决策和试验入组时，有必要进行进一步的研究以确定EGFR蛋白表达是否比EGFR扩增更好的生物标志物。