部分启动子甲基化对异柠檬酸脱氢酶野生型胶质母细胞瘤患者的预测价值。
The predictive value of partial promoter methylation for IDH-wild-type glioblastoma patients.
作者信息
Torre Matthew, Wen Patrick Y, Iorgulescu J Bryan
机构信息
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School; Boston, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School; Boston, MA, USA.
出版信息
Neurooncol Pract. 2022 Sep 10;10(2):126-131. doi: 10.1093/nop/npac070. eCollection 2023 Apr.
BACKGROUND
Glioblastoma patients with hypermethylation of the O-methylguanine-methyltransferase () gene promoter have significantly improved survival when treated with temozolomide compared to patients with unmethylation of the promoter. However, the prognostic and predictive significance of partial promoter methylation is unclear.
METHODS
The National Cancer Database was queried for patients newly diagnosed in 2018 with histopathologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma. The overall survival (OS) associated with promoter methylation status was assessed using multivariable Cox regression with Bonferroni correction for multiple testing ( < .008 was significant).
RESULTS
Three thousand eight hundred twenty-five newly diagnosed IDH-wildtype glioblastoma patients were identified. The promoter was unmethylated in 58.7% ( = 2245), partially methylated in 4.8% ( = 183), hypermethylated in 3.5% ( = 133), and methylated not otherwise specified (NOS; likely consisting predominantly of hypermethylated cases) in 33.0% ( = 1264) of cases. Among patients that received first-line single-agent chemotherapy (ie likely temozolomide), compared to partial methylation (referent), promoter unmethylation was associated with worse OS (hazard ratio [HR] 1.94; 95% confidence interval [95 CI]: 1.54-2.44; < .001) in multivariable Cox regression adjusted for major prognostic confounders. In contrast, a significant OS difference was not observed between partially methylated promoters and either hypermethylated (HR 1.02; 95 CI: 0.72-1.46; = .90) or methylated NOS (HR 0.99; 95 CI: 0.78-1.26; = .93) promoters. Among IDH-wildtype glioblastoma patients who did not receive first-line chemotherapy, promoter methylation status was not associated with significant differences in OS ( = 0.39-0.83).
CONCLUSIONS
Compared to promoter unmethylation, partial methylation was predictive of improved OS among IDH-wildtype glioblastoma patients treated with first-line single-agent chemotherapy-supporting the use of temozolomide therapy in these patients.
背景
与O - 甲基鸟嘌呤 - 甲基转移酶（MGMT）基因启动子未甲基化的胶质母细胞瘤患者相比，MGMT基因启动子甲基化的胶质母细胞瘤患者在接受替莫唑胺治疗时生存期显著延长。然而，部分MGMT启动子甲基化的预后和预测意义尚不清楚。
方法
在国家癌症数据库中查询2018年新诊断的、经组织病理学证实为异柠檬酸脱氢酶（IDH）野生型胶质母细胞瘤的患者。使用多变量Cox回归评估与MGMT启动子甲基化状态相关的总生存期（OS），并采用Bonferroni校正进行多重检验（P <.008为显著）。
结果
共确定3825例新诊断的IDH野生型胶质母细胞瘤患者。MGMT启动子未甲基化的患者占58.7%（n = 2245），部分甲基化的患者占4.8%（n = 183），高度甲基化的患者占3.5%（n = 133），甲基化情况未另作说明（NOS；可能主要由高度甲基化病例组成）的患者占33.0%（n = 1264）。在接受一线单药化疗（即可能为替莫唑胺）的患者中，在针对主要预后混杂因素进行多变量Cox回归调整后，与部分甲基化（参照）相比，MGMT启动子未甲基化与较差的OS相关（风险比[HR] 1.94；95%置信区间[95 CI]：1.54 - 2.44；P <.001）。相比之下，未观察到部分甲基化启动子与高度甲基化启动子（HR 1.02；95 CI：0.72 - 1.46；P =.90）或甲基化情况未另作说明的启动子（HR 0.99；95 CI：0.78 - 1.26；P =.93）之间的OS存在显著差异。在未接受一线化疗的IDH野生型胶质母细胞瘤患者中，MGMT启动子甲基化状态与OS的显著差异无关（P = 0.39 - 0.83）。
结论
与MGMT启动子未甲基化相比，部分甲基化可预测接受一线单药化疗的IDH野生型胶质母细胞瘤患者的OS改善，支持在这些患者中使用替莫唑胺治疗。
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