Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, 710038, China.
Department of Medical Image Diagnosis, Hanzhong Central Hospital, Hanzhong, Shaanxi, 723000, China.
BMC Cancer. 2018 Feb 21;18(1):215. doi: 10.1186/s12885-018-4114-2.
The methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma(GBM). Using pre-operative MRI techniques to predict MGMT promoter methylation status remains inconclusive. In this study, we investigated the value of features from structural and advanced imagings in predicting the methylation of MGMT promoter in primary glioblastoma patients.
Ninety-two pathologically confirmed primary glioblastoma patients underwent preoperative structural MR imagings and the efficacy of structural image features were qualitatively analyzed using Fisher's exact test. In addition, 77 of the 92 patients underwent additional advanced MRI scans including diffusion-weighted (DWI) and 3-diminsional pseudo-continuous arterial spin labeling (3D pCASL) imaging. Apparent diffusion coefficient (ADC) and relative cerebral blood flow (rCBF) values within the manually drawn region-of-interest (ROI) were calculated and compared using independent sample t test for their efficacies in predicting MGMT promoter methylation. Receiver operating characteristic curve (ROC) analysis was used to investigate the predicting efficacy with the area under the curve (AUC) and cross validations. Multiple-variable logistic regression model was employed to evaluate the predicting performance of multiple variables.
MGMT promoter methylation was associated with tumor location and necrosis (P < 0.05). Significantly increased ADC value (P < 0.001) and decreased rCBF (P < 0.001) were associated with MGMT promoter methylation in primary glioblastoma. The ADC achieved the better predicting efficacy than rCBF (ADC: AUC, 0.860; sensitivity, 81.1%; specificity, 82.5%; vs rCBF: AUC, 0.835; sensitivity, 75.0%; specificity, 78.4%; P = 0.032). The combination of tumor location, necrosis, ADC and rCBF resulted in the highest AUC of 0.914.
ADC and rCBF are promising imaging biomarkers in clinical routine to predict the MGMT promoter methylation in primary glioblastoma patients.
氧 6- 甲基鸟嘌呤 -DNA 甲基转移酶(MGMT)启动子的甲基化状态与胶质母细胞瘤(GBM)的治疗反应相关。使用术前 MRI 技术预测 MGMT 启动子甲基化状态仍不确定。在这项研究中,我们研究了结构和高级成像特征在预测原发性胶质母细胞瘤患者 MGMT 启动子甲基化中的价值。
92 例经病理证实的原发性胶质母细胞瘤患者接受术前结构 MRI 检查,并使用 Fisher 精确检验定性分析结构图像特征。此外,92 例患者中有 77 例接受了额外的高级 MRI 扫描,包括弥散加权(DWI)和三维伪连续动脉自旋标记(3D pCASL)成像。在手动绘制的感兴趣区(ROI)内计算表观扩散系数(ADC)和相对脑血流(rCBF)值,并使用独立样本 t 检验比较其在预测 MGMT 启动子甲基化中的效能。使用受试者工作特征曲线(ROC)分析评估曲线下面积(AUC)和交叉验证的预测效能。使用多变量逻辑回归模型评估多个变量的预测性能。
MGMT 启动子甲基化与肿瘤位置和坏死有关(P < 0.05)。原发性胶质母细胞瘤中,MGMT 启动子甲基化与 ADC 值升高(P < 0.001)和 rCBF 降低(P < 0.001)显著相关。ADC 比 rCBF 具有更好的预测效能(ADC:AUC,0.860;敏感性,81.1%;特异性,82.5%;vs rCBF:AUC,0.835;敏感性,75.0%;特异性,78.4%;P = 0.032)。肿瘤位置、坏死、ADC 和 rCBF 的组合导致最高 AUC 为 0.914。
ADC 和 rCBF 是有前途的临床常规成像生物标志物,可预测原发性胶质母细胞瘤患者的 MGMT 启动子甲基化。