[Analysis of the difference in MGMT promoter status in gliomas and its significance in prognosis assessment]

Zhonghua Yi Xue Za Zhi. 2023 Feb 21;103(7):526-529. doi: 10.3760/cma.j.cn112137-20221017-02158.
[Article in Chinese]

Abstract

The data of 1 268 newly diagnosed gliomas from the Fourth Ward of Neurosurgery Department of Beijing Tiantan Hospital between April 2013 and March 2022 were retrospectively analyzed. Based on postoperative pathology, the gliomas were divided into groups: oligodendrogliomas (n=308), astrocytomas (n=337) and glioblastomas (n=623). According to the O6-methylguanine-DNA methyl transferase (MGMT) promoter status defined by the 12% of best cut-off value in previous research results, patients were divided into methylation group (n=763) and non-methylation group (n=505). Methylation level [M (Q1, Q3)] in patients with glioblastoma, astrocytoma and oligodendroglioma was 6% (2%, 24%), 17% (10%, 28%) and 29% (19%, 40%), respectively (P<0.001). Compared with non-methylation patients, the progression-free survival (PFS) and overall survival (OS) of glioblastomas patients with methylation of MGMT promoter demonstrated more favorable prognosis [M (Q1, Q3)]) of PFS: 14.0 (6.0, 36.0) months vs 8.0 (4.0, 15.0) months, P<0.001; M (Q1, Q3) of OS: 29.0 (17.0, 60.5) months vs 16.0 (11.0, 26.5) months, P<0.001]. In astrocytomas patients, the PFS was much longer for those with methylation [the median PFS of patients with methylation was not observed at the end of follow-up, but those without methylation showed a median PFS of 46.0 (29.0, 52.0) months] (P=0.001). However, no statistically significant difference was observed in OS [the median OS of patients with methylation was not observed at the end of follow-up, but those without methylation had a median OS of 62.0 (46.0, 98.0) months] (P=0.085). In oligodendrogliomas patients, no statistically significant differences of PFS and OS were observed between patients with methylation and those without methylation. MGMT promoter status was a related factor affecting PFS and OS in glioblastomas (PFS: HR=0.534,95%CI: 0.426-0.668, P<0.001; OS: HR=0.451, 95%CI: 0.353-0.576, P<0.001). Moreover, MGMT promoter status was also a related factor affecting PFS in astrocytomas (HR=0.462, 95%CI: 0.221-0.966, P=0.040), but not for OS (HR=0.664, 95%CI: 0.259-1.690, P=0.389). The methylation level of MGMT promoter differed substantially in different types of gliomas, and the status of MGMT promoter profoundly affected the prognosis of glioblastomas.

回顾性分析2013年4月至2022年3月北京天坛医院神经外科四病区收治的1 268例成人新诊断的胶质瘤患者资料。根据术后病理类型分为星形细胞瘤(308例)、少突胶质细胞瘤(337例)和胶质母细胞瘤(623例)3组。根据既往研究结果中由最佳cut-off值12%界定的MGMT启动子状态,将患者分为甲基化组(763例)和非甲基化组(505例)。胶质母细胞瘤患者甲基化水平[MQ1Q3)]仅为6%(2%,24%),星形细胞瘤为17%(10%,28%),少突胶质细胞瘤最高,为29%(19%,40%)(P<0.001)。在胶质母细胞瘤患者中,MGMT启动子甲基化患者无进展生存期(PFS)和总生存期(OS)均明显长于非甲基化患者[中位PFS:14.0(6.0,36.0)比8.0(4.0,15.0)个月,P<0.001;中位OS,29.0(17.0,60.5)比16.0(11.0,26.5)个月,P<0.001]。在星形细胞瘤患者中,甲基化患者PFS长于非甲基化患者[甲基化组到随访结束,未观测到中位生存期,非甲基化组为 46.0(29.0,52.0)个月,P=0.001],但OS两组比较差异无统计学意义[甲基化组到随访结束,未观测到中位生存期,非甲基化组为62.0(46.0,98.0)个月,P=0.085]。在少突胶质细胞瘤患者中,甲基化和非甲基化患者PFS和OS比较,差异均无统计学意义。MGMT启动子状态是影响胶质母细胞瘤PFS和OS的相关因素(PFS:HR=0.534,95%CI:0.426~0.668,P<0.001;OS:HR=0.451,95%CI:0.353~0.576,P<0.001);是影响星形细胞瘤PFS的相关因素(HR=0.462,95%CI:0.221~0.966,P=0.040),但不是影响OS的相关因素(HR=0.664,95%CI:0.259~1.690,P=0.389)。3组之间MGMT启动子甲基化水平差异明显,MGMT启动子状态对胶质母细胞瘤患者预后影响显著。.

Publication types

  • English Abstract

MeSH terms

  • Astrocytoma*
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Glioblastoma*
  • Glioma* / genetics
  • Humans
  • Oligodendroglioma*
  • Prognosis
  • Retrospective Studies
  • Tumor Suppressor Proteins / genetics

Substances

  • MGMT protein, human
  • DNA Modification Methylases
  • Tumor Suppressor Proteins
  • DNA Repair Enzymes