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

摘要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.

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作者 Ruichao Chai [1] Guanzhang Li [1] Yuqing Liu [1] Kenan Zhang [1] Zheng Zhao [1] Fan Wu [1] Yuzhou Chang [2] Bo Pang [1] Jingjun Li [1] Yangfang Li [1] Tao Jiang [3] Yongzhi Wang [3] 学术成果认领
作者单位 Department of Molecular Neuropathology,Beijing Neurosurgical Institute;Chinese Glioma Genome Atlas Network(CGGA),Capital Medical University,Beijing 100070,China [1] Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China [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 [3]
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DOI 10.20892/j.issn.2095-3941.2020.0179
发布时间 2021-09-22(万方平台首次上网日期,不代表论文的发表时间)
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癌症生物学与医学(英文版)

癌症生物学与医学(英文版)

2021年18卷1期

271-282页

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