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Research ArticleOriginal Article

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

Ruichao Chai, Guanzhang Li, Yuqing Liu, Kenan Zhang, Zheng Zhao, Fan Wu, Yuzhou Chang, Bo Pang, Jingjun Li, Yangfang Li, Tao Jiang and Yongzhi Wang
Cancer Biology & Medicine February 2021, 18 (1) 271-282; DOI: https://doi.org/10.20892/j.issn.2095-3941.2020.0179
Ruichao Chai
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Guanzhang Li
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Yuqing Liu
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Kenan Zhang
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Zheng Zhao
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Fan Wu
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Yuzhou Chang
2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
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Bo Pang
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Jingjun Li
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Yangfang Li
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
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Tao Jiang
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
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  • For correspondence: [email protected] [email protected]
Yongzhi Wang
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute; Chinese Glioma Genome Atlas Network (CGGA), Capital Medical University, Beijing 100070, China
2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
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  • For correspondence: [email protected] [email protected]
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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

  • Glioblastoma
  • O6methylguanine-DNA methyltransferase
  • isocitrate dehydrogenase
  • temozolomide
  • pyrosequencing

Footnotes

  • ↵*These authors contributed equally to this work.

  • Conflict of interest statement No potential conflicts of interest are disclosed.

  • Received April 17, 2020.
  • Accepted August 11, 2020.
  • Copyright: © 2021, Cancer Biology & Medicine
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY) 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

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Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma
Ruichao Chai, Guanzhang Li, Yuqing Liu, Kenan Zhang, Zheng Zhao, Fan Wu, Yuzhou Chang, Bo Pang, Jingjun Li, Yangfang Li, Tao Jiang, Yongzhi Wang
Cancer Biology & Medicine Feb 2021, 18 (1) 271-282; DOI: 10.20892/j.issn.2095-3941.2020.0179

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Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma
Ruichao Chai, Guanzhang Li, Yuqing Liu, Kenan Zhang, Zheng Zhao, Fan Wu, Yuzhou Chang, Bo Pang, Jingjun Li, Yangfang Li, Tao Jiang, Yongzhi Wang
Cancer Biology & Medicine Feb 2021, 18 (1) 271-282; DOI: 10.20892/j.issn.2095-3941.2020.0179
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Subjects

  • Brain Tumor

Keywords

  • Glioblastoma
  • O6methylguanine-DNA methyltransferase
  • isocitrate dehydrogenase
  • temozolomide
  • pyrosequencing

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