Association of DNA Repair Gene O6-Methylguanine-DNA Methyltransferase (MGMT) Expression with Aberrant Promoter Methylation in Lung Cancer Progression

Background: DNA repair protein O6-methylguanine DNA methyltransferase(MGMT) plays a protective role in lung cancer (LC) by removing the alkyl adducts from the O6 position of damaged guanine. Loss of expression of MGMT gene is rarely induced due to deletion, mutation, or rearrangement of the gene. However aberrant promotor methylation of CpG island of MGMT gene may be also the reason for gene silencing in LC. Aims and Objectives: We aimed to detect the aberrant promoter methylation frequency of MGMT gene and relative mRNA expression in blood samples of LC patients using Methylation Specific PCR(MS-PCR) and Real-Time PCR. Materials and Methods: Gene promoter methylation frequency of MGMT was performed using MS-PCR in overall 49 patients of LC(10 SCLC and 39 NSCLC) and 49 healthy control. mRNA expressions of MGMT gene were evaluated using Real-Time PCR. Statistical analysis was performed to find the association between gene expression and methylation. Results: The expression of MGMT genes was significantly down-regulated in SCLC (3.2 fold) and NSCLC (4.5 fold), in contrast, the promotor methylation frequency of MGMT was higher in SCLC(54%) and NSCLC(61%) as compared to control(40%) with overall odd ratio(OR-3.67; 95% CI = 1.49–9.01; P=0.0047). Pearson correlation between methylation and gene expression was negative (P= 0.002, r= -0.7861). Conclusions: Our finding concluded that the MGMT gene expression was downregulated and negatively associated with higher aberrant promoter methylation in SCLC and NSCLC. Hence, analysis of aberrant promoter methylation of MGMT gene in blood samples could be used as a biomarker of lung cancer detection.