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

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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