The effects of O6-methyl guanine DNA-methyl transferase promotor methylation and CpG1, CpG2, CpG3 and CpG4 methylation on treatment response and their prognostic significance in patients with glioblastoma

Abstract

This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O⁶- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p = 0.02; OR: 0.662,95% CI: 0.430-1019, p = 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p = 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p = 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.