The Change Of Mgmt Gene Expression In Glioma Patients Was Affected By Methylation Regulation And In The Treatment Of Alkylation Agent

Glioma is a common malignant tumor in the brain that severely threatens public health. DNA methylation is a manifestation of epigenetics and the MGMT gene correlates with cell metabolism. Previous studies showed the involvement of MGMT methylation in the malignancy of various tumors. This study focused on the role of the MGMT methylation level and its role in the treatment of glioma by alkylating agents. Human neuroglioma cell line SHG-44 was treated with 5, 10, and 20 mu M 5-Aza-CdR, followed by a qRT-PCR analysis of the MGMT mRNA expression level. Pyrophosphate sequencing was performed to analyze the methylation level of the MGMT gene. A total of 89 neuroglioma patients in our hospital from Jan 2014 to Feb 2017 were recruited for measuring the methylation level in the promoter region of the MGMT gene using the pyrophosphate sequencing approach. Gene methylation levels were compared at 1, 3, 6, and 12 months after drug treatment (temozolomide and nimustine). Treatment with 5-Aza-CdR gradually increased MGMT mRNA expression in a dose-dependent manner, and the MGMT mRNA level was negatively correlated with the methylation level. MGMT gene methylation showed statistical significance among patients across age, smoking, and drinking history. Those patients with more advanced tumor stages presented with higher methylation levels (P<0.05). Glioma patients presented a decreased trend of MGMT methylation levels with an elongated treatment duration. MGMG expression is under the regulation of methylation in glioma cells and is correlated with the efficacy of alkylating drugs.