脑胶质瘤患者MGMT启动子甲基化和IDH1突变与临床预后相关

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (10): 1476-1480.

脑胶质瘤患者MGMT启动子甲基化和IDH1突变与临床预后相关

张宁¹, 马辉辉^1*, 王凡¹, 梁伟¹, 汪义纯¹, 吴炳山², 李庆新²

安徽医科大学第一附属医院 1.肿瘤放射治疗科; 2.神经外科,安徽合肥 230022

收稿日期:2020-11-09 修回日期:2021-01-09 发布日期:2021-09-29
通讯作者: *mahui200@126.com
基金资助:
中华国际医学交流基金(Z-2014-06-19412)

Correlations of MGMT promoter methylation and IDH1 mutations with the clinical prognosis of malignant glioma patients

ZHANG Ning¹, MA Hui-hui^1*, WANG Fan¹, LIANG Wei¹, WANG Yi-chun¹, WU Bing-shan², LI Qing-xin²

1. Department of Radiotherapy; 2. Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

Received:2020-11-09 Revised:2021-01-09 Published:2021-09-29
Contact: *mahui200@126.com

摘要/Abstract

摘要： 目的本研究回顾性分析MGMT、IDH1在脑胶质瘤患者中的突变及表达状况,探讨二者共表达与临床预后之间的关系。方法将放射治疗科2017年10月至2019年10月收治的25例脑胶质瘤术后患者纳入本研究;采用Kaplan-Meier法分析生存率;Log-rank法进行单因素分析。结果 MGMT启动子甲基化患者(χ²=4.22,P＜0.05)较非甲基化者的总生存期(OS)明显延长,MGMT甲基化患者较非甲基化患者的疾病无进展生存时间(PFS)、IDH1阳性患者的OS、PFS较阴性患者无明显延长。MGMT甲基化联合IDH1突变患者较MGMT非甲基化联合IDH1无突变患者生存期明显延长 (P＜0.05)。结论脑胶质瘤术后患者的MGMT甲基化及IDH1基因水平与OS、PFS显著相关,是影响患者临床预后的重要因素。

关键词: 胶质瘤, MGMT, IDH1, 突变, 预后

Abstract: Objective To analyze retrospectively the IDH1 mutation and MGMT promoter methylation of malignant glioma patients and to identify potential relation to clinical situation. Methods Twenty-five patients with glioma who were received treatment from October 2017 to October 2019 were selected; the survival rate was calculated by Kaplan-Meier method and analyzed by Log-Rank test. Results Univariate analysis showed that negative status of MGMT gene promoter methylation(χ²=4.22,P＜0.05) was an important factor affecting the survival rates of patients, and patients with both negative status of MGMT gene promoter methylation and mutation of IDH1 had a significantly prolonged survival(P＜0.05). Conclusions IDH mutation and MGMT promoter methylation status are significantly related to the prognosis of malignant glioma patients.

Key words: glioma, MGMT, IDH1, mutation, prognosis

中图分类号:

R739.41

张宁, 马辉辉, 王凡, 梁伟, 汪义纯, 吴炳山, 李庆新. 脑胶质瘤患者MGMT启动子甲基化和IDH1突变与临床预后相关[J]. 基础医学与临床, 2021, 41(10): 1476-1480.

ZHANG Ning, MA Hui-hui, WANG Fan, LIANG Wei, WANG Yi-chun, WU Bing-shan, LI Qing-xin. Correlations of MGMT promoter methylation and IDH1 mutations with the clinical prognosis of malignant glioma patients[J]. Basic & Clinical Medicine, 2021, 41(10): 1476-1480.

参考文献

[1]Ostrom QT,Cioffi G Gileleman H, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011-2015[J]. Neuro Oncol, 2018, (suppl 4): iv1-iv86.
[2]《中国中枢神经系统胶质瘤诊断和治疗指南》编写组. 中国中枢神经系统胶质瘤诊断与治疗指南(2015)[J]. 中华医学杂志, 2016, 96: 485-509.
[3]曾瑄, 梁智勇. 分子病理在肿瘤个体化医疗发展中的地位和作用[J]. 中华病理学杂志, 2016, 45: 3-5.
[4]郭晓鹏,高路,汪强, 等.循环肿瘤DNA在胶质瘤研究中的进展[J].基础医学与临床,2016, 36:1030-1034.
[5]Esteller M, Toyota M, Sanchez-Cespedes M, et al. Inactivation of the DNA repair gene o6-Methylguanine-DNA methyltransferase by promoter hypermethylation is associa-ted with G to a mutations in k-ras in colorectal tumorigenesis[J]. Cancer Res, 2000, 60:2368-2371.
[6]Schulze E, Knab F, Radke J, et al. Prognostic relevance of tumor purity and TERT promoter mutations on MGMT promoter methylation in glioblastoma[J]. Mol Cancer Res, 2017, 15:532-540.
[7]Tang K, Jin Q, Yan W, et al. Clinical correlation of MGMT protein expression and promoter methylation in Chinese glioblastoma patients[J]. Med Oncol, 2012, 29:1292-1296.
[8]韩雪涛, 周欢娣, 薛晓英, 等. MGMT启动子甲基化对神经胶质瘤患者治疗及预后的临床意义[J]. 中国肿瘤临床, 2019, 46:645-648.
[9]杜希越, 薛晓英, 盖晓惠, 等. 脑胶质瘤分子标志物IDH1R132突变、MGMT和Ki-67与病理分级及预后关系的研究[J]. 安徽医科大学学报, 2017,52: 417-421.
[10]Moradi M, Bahrami A, Shahidsales S, et al. The prognostic value of MGMT promoter methylation in glioblastoma: a meta-analysis of clinical trials[J]. J Cell Physio, 2018, 233: 378-386.
[11]Capper D, Weissert S, JörgBalss, et al. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors[J]. Brain Patho, 2009, 20: 245-254.
[12]Chen JR, Yao Y, Xu HZ, et al. Isocitrate dehydrogenase (IDH)1/2 mutations as prognostic markers in patients with glioblastomas[J]. Medicine, 2016, 95: e2583.doi:10.1097/MD.0000000000002583.
[13]Molenaar RJ, Verbaan D, Lamba S, et al. The combina-tion of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone[J]. Neuro Oncol, 2014, 16:1263-1273.
[14]朱潇鹏, 唐军海, 黄国浩, 等. IDH1突变和MGMT基因启动子甲基化在脑胶质瘤中表达及关联度分析[J]. 中国神经精神疾病杂志, 2015,41: 111-114.
[15]Waitkus MS, Diplas BH, Yan H. Editor's choice, isocitrate dehydrogenase mutations in gliomas[J]. Neuro Oncol, 2016,18: 16-26.
[16]Ogura R, Tsukamoto Y, Natsumeda M, et al. Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for prognostication of patients with diffuse gliomas[J]. Neuropathology, 2015, 35: 324-335.