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二甲双胍的使用与 MGMT 基因沉默的胶质母细胞瘤患者的生存时间延长有关。

Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing.

机构信息

Faculty of Medicine, McGill University, Montreal, Canada.

Neuro-Oncology Research Group, National Institute of Cancer, Bogotá, Colombia.

出版信息

J Neurooncol. 2023 Oct;165(1):209-218. doi: 10.1007/s11060-023-04485-2. Epub 2023 Oct 27.

Abstract

PURPOSE

New treatments are needed to improve the overall survival of patients with glioblastoma Metformin is known for anti-tumorigenic effects in cancers, including breast and pancreas cancers. In this study, we assessed the association between metformin use and overall survival in glioblastoma patients.

METHODS

We retrospectively studied 241 patients who underwent surgery at diagnosis of glioblastoma between 2014 and 2018. Metformin was used for pre-existing type 2 diabetes mellitus or in the prevention or management of glucocorticoid induced hyperglycemia. Kaplan-Meier curves and log-rank p test were used for univariate analysis. Cox-proportional hazards model was used to generate adjusted hazard ratios for multivariate analysis.

RESULTS

Metformin use was associated with longer survival in patients with tumors that had a methylated O6-methylguanine DNA methyltransferase gene (MGMT) promoter (484 days 95% CI: 56-911 vs. 394 days 95% CI: 249-538, Log-Rank test: 6.5, p = 0.01). Cox regression analysis shows that metformin associates with lower risk of death at 2 years in patients with glioblastoma containing a methylated MGMT promoter (aHR = 0.497, 95% CI 0.26-0.93, p = 0.028).

CONCLUSION

Our findings suggest a survival benefit with metformin use in patients with glioblastomas having methylation of the MGMT promoter.

摘要

目的

需要新的治疗方法来提高胶质母细胞瘤患者的总生存率。二甲双胍已被证明具有抗肿瘤作用,可用于治疗乳腺癌和胰腺癌等癌症。在本研究中,我们评估了使用二甲双胍与胶质母细胞瘤患者总生存率之间的关系。

方法

我们回顾性研究了 2014 年至 2018 年间诊断为胶质母细胞瘤并接受手术的 241 名患者。二甲双胍用于治疗 2 型糖尿病或预防或治疗皮质类固醇引起的高血糖症。采用 Kaplan-Meier 曲线和对数秩检验进行单因素分析。采用 Cox 比例风险模型进行多因素分析。

结果

在肿瘤中甲基化 O6-甲基鸟嘌呤 DNA 甲基转移酶基因(MGMT)启动子的患者中,使用二甲双胍与生存时间延长相关(484 天 95%CI:56-911 与 394 天 95%CI:249-538,对数秩检验:6.5,p=0.01)。Cox 回归分析显示,在含有甲基化 MGMT 启动子的胶质母细胞瘤患者中,二甲双胍与 2 年死亡风险降低相关(aHR=0.497,95%CI 0.26-0.93,p=0.028)。

结论

我们的研究结果表明,对于 MGMT 启动子甲基化的胶质母细胞瘤患者,使用二甲双胍可提高生存率。

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