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胶质母细胞瘤中 MGMT 启动子甲基化的预测标志物。

Predictive markers for MGMT promoter methylation in glioblastomas.

机构信息

Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Department of Diagnostic Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

出版信息

Neurosurg Rev. 2019 Dec;42(4):867-876. doi: 10.1007/s10143-018-01061-5. Epub 2019 Jan 23.

DOI:10.1007/s10143-018-01061-5
PMID:30673883
Abstract

The promoter methylation status of the O-methylguanine-DNA methyltransferase (MGMT) gene has been described as the most important predictor of chemotherapeutic response and patients' survival in glioblastomas (GBs). Therefore, prediction of the MGMT promoter methylation status by imaging would help to preoperatively decide the overall treatment strategy as well as surgical strategy. This study aimed to detect imaging parameters to predict MGMT promoter methylation in GBs by using a commercially available software. We investigated three imaging features (ring enhancement, tumor location, and laterality) and apparent diffusion coefficient (ADC) parameters in 48 newly diagnosed GBs treated at Keio University Hospital in 2006 or later. For ADC, texture analyses were performed. Regions of interest (ROIs) were drawn manually with reference to contrast-enhanced areas, excluding necrotic and cystic regions. Mean ADC value and ADC histogram parameters, including kurtosis, skewness, and entropy, were compared with MGMT promoter methylation. Each parameter was evaluated to determine correlation with MGMT promoter methylation, and the parameters with significant associations with the methylation status were correlated with the MGMT-positive cell ratio determined by immunohistochemistry (IHC) analysis. The mean ADC value and ADC entropy were significantly associated with MGMT promoter methylation. The combination of mean ADC value and ADC entropy predicted MGMT promoter methylation, with a PPV of 81.2% and specificity of 88.9%. The mean ADC value and ADC entropy were negatively correlated with the MGMT-positive cell ratio in the IHC analysis. This study demonstrated that texture analyses of ADC histograms in GBs were predictive of MGMT promoter methylation.

摘要

O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)基因的启动子甲基化状态已被描述为胶质母细胞瘤(GBs)化疗反应和患者生存的最重要预测因子。因此,通过影像学预测 MGMT 启动子甲基化状态有助于术前决定整体治疗策略以及手术策略。本研究旨在使用商业上可用的软件检测影像学参数,以预测 GBs 中的 MGMT 启动子甲基化。我们研究了在 2006 年或之后在庆应义塾大学医院接受治疗的 48 例新诊断的 GBs 中的三种影像学特征(环形增强、肿瘤位置和侧别)和表观扩散系数(ADC)参数。对于 ADC,进行了纹理分析。使用 ROI 手动绘制 ROI,参考增强区域,排除坏死和囊性区域。比较平均 ADC 值和 ADC 直方图参数,包括峰度、偏度和熵,与 MGMT 启动子甲基化。评估每个参数与 MGMT 启动子甲基化的相关性,并将与甲基化状态显著相关的参数与免疫组织化学(IHC)分析确定的 MGMT 阳性细胞比率相关联。平均 ADC 值和 ADC 熵与 MGMT 启动子甲基化显著相关。平均 ADC 值和 ADC 熵的组合可预测 MGMT 启动子甲基化,具有 81.2%的阳性预测值和 88.9%的特异性。平均 ADC 值和 ADC 熵与 IHC 分析中的 MGMT 阳性细胞比率呈负相关。本研究表明,GBs 中 ADC 直方图的纹理分析可预测 MGMT 启动子甲基化。

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