Abstract

BACKGROUND: The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. The miRNA-181 family is the important role of radio- and chemo-resistant in glioblastoma (GBM) patients. Our research is to analyze the prognostic significance of MGMT promoter methylation status and miRNA-181 family expression in a group of GBM patients treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. METHODS: Sixty-three patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and miRNA-181 family. We examined methylation status of MGMT promoter by methylation-specific real-time PCR. MiRNA-181 family expression was assessed qPCR. Overall and progression-free survival was calculated according to the Kaplan–Meier method. RESULTS: The MGMT gene promoter was found to be methylated in 29 patients (46.0%) and unmethylated in 34 patients (54.0%). MGMT methylation status was significant correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiRNA-181c and miR-181d expression were the predictive markers in GBM patients prognosis (p < 0.05). MiRNA-181c and miRNA-181d were down-regulated in patients who responded to RT/TMZ (p = 0.032; p = 0.017, respectively) in comparison to patients with poor prognosis. Analyses of possible correlation between miRNA-181d expression and MGMT promoter methylation status were positive. CONCLUSIONS: Our results support the hypothesis that MGMT promoter methylation status may be a predictive biomarker in the treatment of patients with GBM. In addition, our data indicate for the first time that expression levels of miRNA-181c and miRNA-181d could serve as a predictive marker of response to RT/TMZ therapy in GBM patients. Moreover, these data suggest that miRNA-181d is a potential role to regulate MGMT promoter methylation status.

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