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.

A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM]

“…There were several limitations within the studies that we identified that may lead to bias or disparity between predicted measure of effect and true measure of effect. Many of these studies had smaller sample sizes, with some using publicly available methylation data to increase their study population [16,18,19]. Apart from studies that employed BeadChip arrays, most studies interrogated select CpG sites within the MGMT CGI, mostly due to the commercial availability of certain PSQ kits.…”

“…The study by Yildiz et al, which has low GRADE scoring, was a Turkish study that examined the prognostic significance of MGMT methylation at 4 CpG islands [18]. However, the author does not specify the location of these "CpG islands" apart from them being located within the MGMT promoter.…”

SFPQ and Its Isoform as Potential Biomarker for Non-Small-Cell Lung Cancer

“…We then explored a possible mechanism for the SFPQ isoform changes seen in lung cancer. DNA methylation is an important factor in cancer development [34][35][36][37][38][39] that can lead to changes in expression [40][41][42]. We have discovered DNA methylation differences in the SFPQ promoter region which may be responsible for the SFPQ isoform expression differences between lung cancer and IPF and normal cells.…”

A Systematic Review of High Impact CpG Sites and Regions for MGMT Methylation in Glioblastoma [A Systematic Review of MGMT Methylation in GBM]

“…The last study included in this systematic review, Yildiz et al was a Turkish study that examined the prognostic signi cance of MGMT methylation at 4 CpG islands 19 . However, the author does not specify the location of these "CpG islands" apart from them being located within the MGMT promoter.…”