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Original Article | Open Access

Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma

Ruichao Chai1,*, Guanzhang Li1,*, Yuqing Liu1, Kenan Zhang1, Zheng Zhao1, Fan Wu1, Yuzhou Chang2, Bo Pang1, Jingjun Li1, Yangfang Li1, Tao Jiang1,2 ( ), Yongzhi Wang1,2 ( )
Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

*These authors contributed equally to this work.

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Abstract

Objective

O6methylguanine-DNA methyltransferase (MGMT) promoter methylation is a biomarker widely used to predict the sensitivity of IDH-wildtype glioblastoma to temozolomide therapy. Given that the IDH status has critical effects on the survival and epigenetic features of glioblastoma, we aimed to assess the role of MGMT promoter methylation in IDH-mutant glioblastoma.

Methods

This study included 187 IDH-mutant glioblastomas and used 173 IDH-wildtype glioblastomas for comparison. Kaplan-Meier curves and multivariate Cox regression were used to study the predictive effects.

Results

Compared with IDH-wildtype glioblastomas, IDH-mutant glioblastomas showed significantly higher (P < 0.0001) MGMT promoter methylation. We demonstrated that MGMT promoter methylation status, as determined by a high cutoff value (≥30%) in pyrosequencing, could be used to significantly stratify the survival of 50 IDH-mutant glioblastomas receiving temozolomide therapy (cohort A); this result was validated in another cohort of 25 IDH-mutant glioblastomas (cohort B). The median progression-free survival and median overall survival in cohort A were 9.33 and 13.76 months for unmethylated cases, and 18.37 and 41.61 months for methylated cases, and in cohort B were 6.97 and 9.10 months for unmethylated cases, and 23.40 and 26.40 months for methylated cases. In addition, we confirmed that the MGMT promoter methylation was significantly (P = 0.0001) correlated with longer OS in IDH-mutant patients with GBM, independently of age, gender distribution, tumor type (primary or recurrent/secondary), and the extent of resection.

Conclusions

MGMT promoter methylation has predictive value in IDH-mutant glioblastoma, but its cutoff value should be higher than that for IDH-wildtype glioblastoma.

Keywords

GlioblastomatemozolomidepyrosequencingO6methylguanine-DNA methyltransferaseisocitrate dehydrogenase

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 18 Issue 1,
February 2021
Pages 271-282
DOI: 10.20892/j.issn.2095-3941.2020.0179
Cite this article:
Chai R, Li G, Liu Y, et al. Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma. Cancer Biology & Medicine, 2021, 18(1): 271-282. https://doi.org/10.20892/j.issn.2095-3941.2020.0179

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Received: 17 April 2020
Accepted: 11 August 2020
Published: 01 February 2021
©2021 Cancer Biology & Medicine.

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