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

Journal of Neuro-oncology
Guoqiang YuanYawen Pan

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%; specifici...Continue Reading

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Citations

Feb 9, 2018·Journal of Behavioral Addictions·Miles RichardsonMark D Griffiths
May 7, 2019·Journal of Neuropathology and Experimental Neurology·Rikke H DahlrotBjarne Winther Kristensen
Mar 27, 2018·Journal of Cellular Biochemistry·Lei Shi, Guan Sun
Oct 7, 2018·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Rui-Chao ChaiYong-Zhi Wang
Oct 29, 2020·International Journal of Cancer. Journal International Du Cancer·Theophilos TzaridisJörg Felsberg

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