胶质瘤中<italic style="font-style: italic">MGMT</italic>甲基化状态及其临床意义的回顾性研究

姜琳; 刘绮颖; 贾利晴; 张静; 常恒; 薛田; 任敏; 柏乾明; 朱晓丽; 周晓燕

doi:10.19401/j.cnki.1007-3639.2023.08.003

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胶质瘤中MGMT甲基化状态及其临床意义的回顾性研究

论著 | 更新时间：2025-12-31

- 胶质瘤中MGMT甲基化状态及其临床意义的回顾性研究
- Retrospective study on MGMT methylation status and its clinical significance in gliomas
- 中国癌症杂志 2023年33卷第8期页码：740-750
- 作者机构：
  
  复旦大学附属肿瘤医院病理科，复旦大学上海医学院肿瘤学系，复旦大学病理研究所，上海 200032
- 作者简介：
  
  [ "姜琳（ORCID: 0000-0003-1873-4152），硕士，初级技师。" ]
  周晓燕（ORCID: 0000-0001-5999-7237），主任医师，教授。
- 基金信息：
  
  上海市协同创新集群(2019CXJQ03);上海市科学技术委员会“ 科技创新行动计划”医学创新研究专项(20Z11900300)
- DOI：10.19401/j.cnki.1007-3639.2023.08.003
  中图分类号： R739.41
- 收稿：2023-04-26，
  
  修回：2023-07-02，
  
  纸质出版：2023-08-30
- 稿件说明：
移动端阅览
姜琳, 刘绮颖, 贾利晴, 等. 胶质瘤中MGMT甲基化状态及其临床意义的回顾性研究[J]. 中国癌症杂志, 2023,33(8):740-750.

Lin JIANG, Qiying LIU, Liqing JIA, et al. Retrospective study on MGMT methylation status and its clinical significance in gliomas[J]. China Oncology, 2023, 33(8): 740-750.
姜琳, 刘绮颖, 贾利晴, 等. 胶质瘤中MGMT甲基化状态及其临床意义的回顾性研究[J]. 中国癌症杂志, 2023,33(8):740-750. DOI： 10.19401/j.cnki.1007-3639.2023.08.003.

Lin JIANG, Qiying LIU, Liqing JIA, et al. Retrospective study on MGMT methylation status and its clinical significance in gliomas[J]. China Oncology, 2023, 33(8): 740-750. DOI： 10.19401/j.cnki.1007-3639.2023.08.003.

摘要

背景与目的：

胶质瘤是中枢神经系统常见且预后较差的恶性肿瘤，手术后联合替莫唑胺（temozolomide，TMZ）同步放化疗是胶质瘤的主要治疗方案。O6-甲基鸟嘌呤DNA甲基转移酶（O6-methylguanine DNA methyltranferase，MGMT）基因启动子甲基化（

MGMT

promoter methylation，

MGMT

met）状态可预测胶质瘤患者对TMZ治疗的敏感性，但其与临床病理学特征的关系及如何更好地预测治疗效果及患者预后尚需深入研究。本研究旨在分析胶质瘤中

MGMT

met状态及其与临床病理学特征和其他常见分子异常的相关性，探讨

MGMT

met与其他分子异常联合分析对胶质瘤患者预后和TMZ治疗效果判断的价值。

方法：

回顾性收集复旦大学附属肿瘤医院病理科2019年7月—2022年9月诊断的205例胶质瘤患者的临床病理学资料，采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）法检测

MGMT

met状态；采用Sanger测序法检测异柠檬酸脱氢酶（isocitrate dehydrogenase，IDH）1和IDH2端粒酶反转录酶（telomerase reverse transcriptase，TERT）基因突变情况；采用荧光原位杂交（fluorescence

in situ

hybridization，FISH）检测1号染色体短臂和19号染色体长臂（the short arm of chromosome 1 and the long arm of chromosome 19，1p19q）缺失情况。

结果：

205例患者中，女性患者的

MGMT

met发生率高于男性。相比于胶质母细胞瘤（47.3%），星形细胞瘤（74.1%）和少突胶质细胞瘤（100.0%）中

MGMT

基因启动子更易发生甲基化（

0.05）。在

MGMT

met组中，

IDH

1突变（mutant，mut）率和1p19q共缺失（co-deletion，co-del）率明显提高，且

MGMT

met与

IDH

1mut和1p19qco-del具有相关性（

0.05）。

MGMT

met、年龄小于55岁、少突胶质细胞瘤及世界卫生组织（World Health Organization，WHO） 1~3级的患者均表现出较长的总生存期（overall survival，OS），差异有统计学意义（

0.05）。相比于单个影响因素，双/三基因联合分析[

MGMT

met/

IDH

1mut、

MGMT

met/1p19q co-del或

MGMT

met/

IDH

1mut/1p19q co-del

]

预测患者预后的效果更好（

0.05），后两者是独立预后因素。在TMZ治疗患者中，

MGMT

met（

MGMT

met/TMZ+）患者比其他组预后好，如果患者联合存在

IDH

1mut，患者预后得到进一步提高（

0.05）。

结论：

MGMT

met好发于女性和少突胶质细胞瘤患者中；其与

IDH

1mut及1p19 qco-del呈正相关。

MGMT

met的患者与TMZ治疗效果及预后较好有关，且

MGMT

met联合

IDH

突变和1p19q co-del分析可能具有更好的TMZ治疗效果和预后提示价值。

Abstract

Background and purpose:

Glioma is a common malignant tumor of central nervous system with poor prognosis. Postoperative concurrent chemoradiotherapy with temozolomide (TMZ) is the main treatment for glioma. The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter can predict the sensitivity of glioma patients to TMZ treatment

however its relationship with clinical pathology and how to better predict treatment and prognosis still need further research. The purpose of this study was to analyze the status of

MGMT

promoter methylation (

MGMT

met) in gliomas and its correlation with clinical pathological features and other common molecular abnormalities

and to explore the value of combined analysis of

MGMT

met and other molecular abnormalities in predicting the prognosis of glioma and the efficacy of TMZ treatment.

Methods:

We retrospectively collected clinical and pathological data from 205 glioma patients diagnosed by the Department of Pathology

Fudan University Shanghai Cancer Center from Ju

ly 2019 to September 2022. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect

MGMT

met status. Sanger sequencing was used to detect the mutation of isocitrate dehydrogenase 1 and 2 (

IDH

1/2) and telomerase reverse transcriptase (TERT) genes. Fluorescence

in situ

hybridization (FISH) was used to detect the deletion of the short arm of chromosome 1 and the long arm of chromosome 19 (1p19q).

Results:

Among 205 patients

the incidence of

MGMT

met was higher in female patients than in male patients. Compared to glioblastoma (47.3%)

astrocytoma (74.1%) and oligodendroglioma (100.0%) were more prone to methylation of the

MGMT

gene promoter (

0.05). In

MGMT

met group

IDH1 mutation rate and 1p19q co-deletion rate were significantly increased

and methylation of

MGMT

promoter was correlated with IDH1 mutation and 1p19q co-deletion (

0.05). Patients with

MGMT

met

age less than 55 years

oligodendroglioma

and World Health Organization (WHO) grade 1-3 all showed longer overall survival (OS)

and the difference is statistically significant (

0.05). Compared with individual influencing factors

dual/triple gene combination analysis (

MGMT

met/

IDH

1 mutation or

MGMT

met/1p19q co-deletion or

MGMT

met/

IDH

1 mutation/1p19q co-deletion) had better effect for predicting the patient prognosis (

0.05)

with the latter two being independent prognostic factors. Among TMZ treated patients

MGMT

met (MGMTmet/TMZ+) patients had a better prognosis than other groups. If the patients had combined

IDH

1 mutations

the prognosis of the patients was further improved (

0.05).

Conclusion:

MGMT

met is more common in women a

nd patients with oligodendroglioma. It is positively correlated with

IDH

1 mutation and 1p19q co-deletion. Patients with

MGMT

met are associated with better TMZ treatment efficacy and prognosis

and

MGMT

met combined with

IDH

mutations and 1p19q co-deletion analysis have better TMZ treatment efficacy and prognostic implications.

关键词

Keywords

references

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胶质瘤中MGMT甲基化状态及其临床意义的回顾性研究

Retrospective study on MGMT methylation status and its clinical significance in gliomas

DOI：10.19401/j.cnki.1007-3639.2023.08.003

摘要

Abstract

关键词

Keywords

references