Posttreatment Effect of MGMT Methylation Level on Glioblastoma Survival.

ABSTRACT: The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes temozolomide-induced alkylation, thereby preventing DNA damage and cytotoxicity. We investigated the prognostic effect of different MGMT methylation levels on overall and progression-free survival in 327 patients with primary glioblastoma undergoing standard treatment. We obtained MGMT methylation level in 4 CpG sites using pyrosequencing. The association between MGMT methylation level and survival was investigated using Cox proportional hazards model and an extension to detect time-varying effects. We found an association between MGMT methylation level and overall survival (OS) from around 9?months after the diagnosis, with no association between MGMT methylation level and OS before that. For patients surviving at least 9?months even small increases in MGMT methylation level are significantly beneficial (HR?=?0.97, 95% CI [0.96, 0.98]). The predictive ability of MGMT methylation level on OS from 9?months after diagnosis has a Harrel's C of 66%. We conclude that the MGMT methylation level is strongly associated with survival only for patients surviving beyond 9?months with considerable effects for levels much lower than previously reported. Prognostic evaluation of cut-points of MGMT methylation levels and of CpG island site selection should take the time-varying effect on overall survival into account.

SUBMITTER: Dahlrot RH 

PROVIDER: S-EPMC6581556 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature