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01-05-2017 | Clinical Study

Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for clinical setting in glioblastoma patients

Authors: Guoqiang Yuan, Liang Niu, Yinian Zhang, Xiaoqing Wang, Kejun Ma, Hang Yin, Junqiang Dai, Wangning Zhou, Yawen Pan

Published in: Journal of Neuro-Oncology | Issue 1/2017

Abstract

Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in the treatment of glioblastoma (GBM). Hypermethylation in O⁶-methylguanine-DNA methyltransferase (MGMT) promoter is thought to play a critical role in this resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for MGMT promoter methylation testing. The unresolved issue is the determination of a cut-off value for dichotomization of quantitative MGMT PSQ results into “MGMT methylated” and “MGMT unmethylated” patient subgroups as a basis for further treatment decisions. In this study, receiver operating characteristic (ROC) curve analysis was used to identify an optimal cutoff of MGMT promoter methylation by testing mean percentage of methylation of 4 CpG islands (76–79) within MGMT exon 1. The area under the ROC (AUC) as well as the best cutoff to classify the methylation were calculated. Positive likelihood ratio (LR+) was chosen as a diagnostic parameter for defining an optimal cut-off. Meanwhile, we also analyzed whether mean percentage of methylation at the investigated CpG islands could be regarded as a marker for evaluating prognostication. ROC analysis showed that the optimal threshold was 12.5% (sensitivity: 60.87%; specificity: 76%) in response to the largest LR+ 2.54. 12.5% was established to distinguish MGMT promoter methylation, which was confirmed using validation set. According to the cutoff value, the MGMT promoter methylation was found in 58.3% of GBM. Mean methylation level of the investigated CpG sites strong correlated with overall survival (OS), which means GBM patients with a high level of methylation survived longer than those with low level of methylation(log-rank test, P = 0.017). In conclusion, ROC curve analysis enables the best cutoff for discriminating MGMT promoter methylation status. LR+ can be used as a key factor that evaluates cutoff. The promoter methylation level of MGMT by PSQ in GBM patients had prognostic value.

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Title: Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for clinical setting in glioblastoma patients
Authors: Guoqiang Yuan
Liang Niu
Yinian Zhang
Xiaoqing Wang
Kejun Ma
Hang Yin
Junqiang Dai
Wangning Zhou
Yawen Pan
Publication date: 01-05-2017
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-017-2433-9

At a glance: The STEP trials

Springer Medicine

Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for clinical setting in glioblastoma patients

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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