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 |
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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. |
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ISSN: | 2095-3941 |
DOI: | 10.20892/j.issn.2095-3941.2020.0179 |