[1]岳新鹏,李 鑫,刘增强,等.O6-甲基鸟嘌呤-DNA甲基转移酶基因启动子甲基化对脑胶质瘤患者化学治疗敏感性及生存的影响[J].新乡医学院学报,2022,39(3):238-242.[doi:10.7683/xxyxyxb.2022.03.008]
 YUE Xinpeng,LI Xin,LIU Zengqiang,et al.Effect of O6-methylguanine-DNA methyltransferase gene promoter methylation on chemosensitivity and survival of patients with glioma[J].Journal of Xinxiang Medical University,2022,39(3):238-242.[doi:10.7683/xxyxyxb.2022.03.008]
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O6-甲基鸟嘌呤-DNA甲基转移酶基因启动子甲基化对脑胶质瘤患者化学治疗敏感性及生存的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年3
页码:
238-242
栏目:
临床研究
出版日期:
2022-03-05

文章信息/Info

Title:
Effect of O6-methylguanine-DNA methyltransferase gene promoter methylation on chemosensitivity and survival of patients with glioma
作者:
岳新鹏李 鑫刘增强巨 涛赵 茹王鑫超
(延安大学咸阳医院神经外科,陕西 咸阳 712000)
Author(s):
YUE XinpengLI XinLIU ZengqiangJU TaoZHAO RuWANG Xinchao
(Department of Neurosurgery,Xianyang Hospital,Yan′an University,Xianyang 712000,Shaanxi Province,China)
关键词:
脑胶质瘤O6-甲基鸟嘌呤-DNA甲基转移酶甲基化化学治疗敏感性
Keywords:
gliomaO6-methylguanine-DNA methyltransferasemethylationchemotherapysensitivity
分类号:
R739.41
DOI:
10.7683/xxyxyxb.2022.03.008
文献标志码:
A
摘要:
目的 探讨O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子甲基化对脑胶质瘤患者化学治疗敏感性及生存的影响。方法 选择2014年1月至2017年8月延安大学咸阳医院收治的90例脑胶质瘤患者为研究对象,所有患者进行手术切除胶质瘤,术后给予同步放射治疗、化学治疗联合替莫唑胺辅助化学治疗。采用甲基化特异性聚合酶链反应(MSP)检测患者胶质瘤组织和瘤旁组织中MGMT基因启动子甲基化水平,比较肿瘤组织与瘤旁组织中的MGMT基因启动子甲基化阳性率。所有患者术后随访36个月,比较复发与未复发患者的MGMT基因启动子甲基化阳性率,比较MGMT基因启动子甲基化阳性与阴性患者的无进展生存期(PFS)和总生存期(OS)。采用Kaplan-Meier法绘制生存曲线,单因素和多因素Cox回归模型分析脑胶质瘤患者生存的影响因素。结果 90例脑胶质瘤患者中,胶质瘤组织和瘤旁组织中MGMT基因启动子甲基化阳性率分别为43.33%(39/90)、4.44%(4/90),胶质瘤组织中MGMT基因启动子甲基化阳性率显著高于瘤旁组织(χ2=37.430,P<0.05)。75例复发患者胶质瘤组织中MGMT基因启动子甲基化阳性率为42.86%(30/70),15例未复发患者胶质瘤组织中MGMT基因启动子甲基化阳性率为60.00%(9/15),复发患者胶质瘤组织中MGMT基因启动子甲基化阳性率显著低于未复发患者(χ2=6.978,P<0.05)。39例胶质瘤组织中MGMT基因启动子甲基化阳性患者的PFS、OS分别为(58.69±3.36)、(82.36±4.56)周,51例胶质瘤组织中MGMT基因启动子甲基化阴性患者的PFS、OS分别为(52.74±3.08)、(78.76±4.01)周;胶质瘤组织中MGMT基因启动子甲基化阳性患者的PFS、OS显著长于阴性患者(t=8.730、3.932,P<0.05)。截至术后36个月,90例患者中存活28例,死亡62例。单因素分析结果显示,年龄、手术切除方式、肿瘤临床分期、MGMT基因启动子甲基化状态与脑胶质瘤患者生存有关(P<0.05),而性别、肿瘤直径、Karnofsky评分、肿瘤组织学类型、肿瘤部位与脑胶质瘤患者生存无关(P>0.05)。Cox回归模型分析显示,年龄>40岁、手术次全切是影响脑胶质瘤患者生存的独立危险因素(P<0.05),MGMT基因启动子甲基化是脑胶质瘤患者生存的保护因素(P<0.05)。结论 MGMT基因启动子甲基化可提高脑胶质瘤患者的化学治疗敏感性,是患者生存的保护因素。
Abstract:
Objective To investigate the effect of O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation on chemosensitivity and survival of patients with glioma.Methods A total of 90 patients with glioma who admitted to Xianyang Hospital of Yan′an University from January 2014 to August 2017 were selected as the research subjects.All patients underwent surgical resection of gliomas,and received concurrent chemoradiation combined with temozolomide adjuvant chemotherapy after surgery.The methylation level of MGMT gene promoter in glioma tissues and peritumoral tissues was detected by methylation-specific polymerase chain reaction (MSP),and the positive rate of MGMT gene promoter methylation in tumor tissues and peritumoral tissues was compared.All patients were followed up for 36 months after operation,the positive rate of MGMT gene promoter methylation was compared between the recurrence and non-recurrence patients,and the progression free survival (PFS) and overall survival (OS) of patients with positive and negative MGMT gene promoter methylation were compared.The survival curve was drawn by the Kaplan-Meier method,and the survival factors of glioma patients were analyzed by univariate and multivariate Cox regression models.Results Among the 90 glioma patients,the positive rate of MGMT gene promoter methylation in glioma tissues and peritumoral tissues was 43.33% (39/90) and 4.44% (4/90),respectively.The positive rate of MGMT gene promoter methylation in glioma tissues was significantly higher than that in the adjacent tissue (χ2=37.430,P<0.05).The positive rate of MGMT gene promoter methylation in glioma tissues of 75 patients with recurrence was 42.86% (30/70),and the positive rate of MGMT gene promoter methylation in glioma tissues of 15 patients without recurrence was 60.00% (9/15).The positive rate of MGMT gene promoter methylation in glioma tissues of patients with recurrence was significantly lower than that of patients without recurrence (χ2=6.978,P<0.05).The PFS and OS of 39 patients with positive MGMT gene promoter methylation in glioma tissues were (58.69±3.36) and (82.36±4.56) weeks,respectively.The PFS and OS of 51 patients with negative MGMT gene promoter methylation in glioma tissues were (52.74±3.08) and (78.76±4.01) weeks,respectively.The PFS and OS of patients with positive MGMT gene promoter methylation in glioma tissues were significantly longer than those of negative patients (t=8.730,3.932;P<0.05).Up to 36 months after surgery,among the 90 patients,28 patients survived and 62 patients died.Univariate analysis results showed that the age,surgical resection method,tumor clinical stage and MGMT gene promoter methylation were related to the survival of patients with glioma (P<0.05),while the gender,tumor diameter,Karnofsky score,tumor histology type and tumor location were not related to the survival of patients with glioma (P>0.05).Cox regression model analysis showed that the age >40 years old and subtotal resection were the independent risk factors for the survival of patients with glioma (P<0.05),and the MGMT gene promoter methylation was a protective factor for survival of patients with glioma (P<0.05).Conclusion The MGMT gene promoter methylation can improve the sensitivity of glioma patients to chemotherapy,it is a protective factor for the survival of patients with glioma.

参考文献/References:

[1] WANG T J C,MEHTA M P.Low-grade glioma radiotherapy treatment and trials[J].Neurosurg Clin N Am,2019,30(1):111-118.
[2] JIAPAER S,FURUTA T,TANAKA S,et al.Potential strategies overcoming the temozolomide resistance for glioblastoma[J].Neurol Med Chir (Tokyo),2018,58(10):405-421.
[3] 余露山,曾苏.基于表观遗传的摄取型药物转运体表达调控是肿瘤耐药干预的新途径[J].医学研究生学报,2019,32(5):449-454.
YU L S,ZENG S.Epigenetics-based regulation of uptake drug transporter expression is a new approach for cancer drug resistance intervention[J].J Med Postgra,2019,32(5):449-454.
[4] RAO A M,QUDDUSI A,SHAMIM M S.The significance of MGMT methylation in glioblastoma multiforme prognosis[J].J Pak Med Assoc,2018,68(7):1137-1139.
[5] WANG H W,XU Z K,SONG Y,et al.Correlations of MGMT genetic polymorphisms with temozolomide resistance and prognosis of patients with malignant gliomas:a population-based study in China[J].Cancer Gene Ther,2017,24(5):215-220.
[6] 占传家,朱文珍,王承缘.2007年世界卫生组织对于中枢神经系统肿瘤的分类[J].放射学实践,2008,23(2):122-127.
ZHAN C J,ZHU W Z,WANG C Y.2007 WHO classification of tumors of the central nervous system [J].Radiol Pract,2008,23(2):122-127.
[7] 吕爽,张海波,徐莹,等.复发脑胶质瘤再程放疗的远期疗效分析[J].中华放射肿瘤学杂志,2020,29(6):411-415.
LYU S,ZHANG H B,XU Y,et al.Analysis of long-term efficacy of re-irradiation for recurrent glioma[J].Chin J Radiat Oncol,2020,29(6):411-415.
[8] NABORS L B,PORTNOW J,AMMIRATI M,et al.NCCN guidelines insights:central nervous system cancers,version 1.2017[J].J Natl Compr Canc Netw,2017,15(11):1331-1345.
[9] MIYAUCHI J T,TSIRKA S E.Advances in immunotherapeutic research for glioma therapy[J].J Neurol,2018,265(4):741-756.
[10] MA R M,ZHENG G H,SHAO C Q,et al.Downregulation of miR-196b promotes glioma cell sensitivity to temozolomide chemotherapy and radiotherapy[J].Ann Clin Lab Sci,2018,48(6):719-725.
[11] BELL E H,ZHANG P,FISHER B J,et al.Association of MGMT promoter methylation status with survival outcomes in patients with high-risk glioma treated with radiotherapy and temozolomide:an analysis from the NRG oncology/RTOG 0424 trial[J].JAMA Oncol,2018,4(10):1405-1409.
[12] SIGNORELL R D,PAPACHRISTODOULOU A,XIAO J W,et al.Preparation of PEGylated liposomes incorporating lipophilic lomeguatrib derivatives for the sensitization of chemo-resistant gliomas[J].Int J Pharm,2018,536(1):388-396.
[13] 陈鑫,张国琴,阮秀杭,等.基于表观扩散系数直方图分析预测多形性胶质母细胞瘤MGMT基因启动子甲基化状态[J].实用放射学杂志,2020,36(6):965-968.
CHEN X,ZHANG G Q,RUAN X H,et al.ADC-based histogram analysis for prediction of MGMT gene promoter methylation status in glioblastoma multiform[J].J Pract Radiol,2020,36(6):965-968.
[14] 薛智文,王晓叶,魏益群.MGMT基因启动子甲基化与非小细胞肺癌化疗敏感性及预后的关系[J].海南医学院学报,2019,25(14):1083-1086,1091.
XUE Z W,WANG X Y,WEI Y Q.Relationship between methylation of MGMT gene promoter and chemosensitivity and prognosis of non-small cell lung cancer[J].J Hainan Med Univ,2019,25(14):1083-1086,1091.
[15] BINABAJ M 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 Physiol,2018,233(1):378-386.
[16] O′REGAN C J,KEARNEY H,BEAUSANG A,et al.Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol[J].J Neurooncol,2018,137(2):233-240.

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更新日期/Last Update: 2022-03-05