O G Yildiz, D Aslan, H Akalin, Y Erdem, O Canoz, A Aytekin, S Ozoner, M Dundar
{"title":"o6 -甲基鸟嘌呤dna -甲基转移酶启动子甲基化及CpG1、CpG2、CpG3和CpG4甲基化对胶质母细胞瘤患者治疗反应的影响及其预后意义","authors":"O G Yildiz, D Aslan, H Akalin, Y Erdem, O Canoz, A Aytekin, S Ozoner, M Dundar","doi":"10.2478/bjmg-2020-0015","DOIUrl":null,"url":null,"abstract":"<p><p>This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O<sup>6</sup>- 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, <i>p</i> = 0.02; OR: 0.662,95% CI: 0.430-1019, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, <i>p</i> = 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.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.5000,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/af/bjmg-23-033.PMC7474218.pdf","citationCount":"1","resultStr":"{\"title\":\"The Effects of O<sup>6</sup>-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.\",\"authors\":\"O G Yildiz, D Aslan, H Akalin, Y Erdem, O Canoz, A Aytekin, S Ozoner, M Dundar\",\"doi\":\"10.2478/bjmg-2020-0015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O<sup>6</sup>- 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, <i>p</i> = 0.02; OR: 0.662,95% CI: 0.430-1019, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, <i>p</i> = 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. 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引用次数: 1
摘要
本回顾性研究探讨了O6-甲基鸟嘌呤甲基转移酶(MGMT)启动子甲基化和cpg1、CpG2、CpG3和CpG4甲基化在胶质母细胞瘤(GB)术后放疗(PORT)患者中,辅助或不辅助替莫唑胺(TMZ)的预后意义和治疗效果。100例GB患者接受PORT联合TMZ +辅助TMZ或单独PORT治疗。检测CpG1、CpG2、CpG3和CpG4岛的MGMT启动子甲基化。总体而言,mgmt -甲基化成为改善总生存期(OS)和无进展生存期(PFS)的重要预后因素[优势比(OR): 0.609, 95%可信区间(95% CI): 0.395-0.939, p = 0.02;OR: 0.662,95% CI: 0.430-1019, p = 0.5]。CpG1、CpG2、CpG3和CpG4岛的甲基化对OS无显著影响,CpGl、CpG2和CpG4岛的甲基化对PFS无显著影响(p p = 0.04)。在仅接受放疗(RT)的组中,CpG1和CpC3甲基化被发现在PFS方面具有积极的预后意义(OR: 266, 95% CI: 1.05-6.75, CpG1的p -0.03;OR: 2.4, 95% CI: 1.01-5.92, p = 0.04。MGMT启动子甲基化是预测治疗反应的重要生物标志物。个别岛屿,特别是CpG3,值得作为一种预后标志进行进一步调查。进一步的研究需要更大的样本量来澄清结果。
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.
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.
期刊介绍:
Balkan Journal of Medical Genetics is a journal in the English language for publication of articles involving all branches of medical genetics: human cytogenetics, molecular genetics, clinical genetics, immunogenetics, oncogenetics, pharmacogenetics, population genetics, genetic screening and diagnosis of monogenic and polygenic diseases, prenatal and preimplantation genetic diagnosis, genetic counselling, advances in treatment and prevention.