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

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

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Veröffentlicht in:Cancer biology & medicine 2021-02, Vol.18 (1), p.272-282
Hauptverfasser: Chai, Ruichao, Li, Guanzhang, Liu, Yuqing, Zhang, Kenan, Zhao, Zheng, Wu, Fan, Chang, Yuzhou, Pang, Bo, Li, Jingjun, Li, Yangfang, Jiang, Tao, Wang, Yongzhi
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Sprache:eng
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Zusammenfassung:O6methylguanine-DNA methyltransferase ( ) promoter methylation is a biomarker widely used to predict the sensitivity of -wildtype glioblastoma to temozolomide therapy. Given that the status has critical effects on the survival and epigenetic features of glioblastoma, we aimed to assess the role of promoter methylation in -mutant glioblastoma. This study included 187 -mutant glioblastomas and used 173 -wildtype glioblastomas for comparison. Kaplan-Meier curves and multivariate Cox regression were used to study the predictive effects. Compared with -wildtype glioblastomas, -mutant glioblastomas showed significantly higher ( < 0.0001) promoter methylation. We demonstrated that promoter methylation status, as determined by a high cutoff value (≥30%) in pyrosequencing, could be used to significantly stratify the survival of 50 -mutant glioblastomas receiving temozolomide therapy (cohort A); this result was validated in another cohort of 25 -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 promoter methylation was significantly ( = 0.0001) correlated with longer OS in -mutant patients with GBM, independently of age, gender distribution, tumor type (primary or recurrent/secondary), and the extent of resection. promoter methylation has predictive value in -mutant glioblastoma, but its cutoff value should be higher than that for -wildtype glioblastoma.
ISSN:2095-3941
DOI:10.20892/j.issn.2095-3941.2020.0179