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胶质母细胞瘤和其他胶质瘤患者的异柠檬酸脱氢酶(IDH)突变及O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)甲基化状态:一项俄罗斯回顾性队列研究

IDH mutation and MGMT methylation status in glioblastoma and other gliomas patients: a Russian retrospective cohort study.

作者信息

Eid Moez, Alset Dema, Timoshkina Nataliya, Gvaldin Dmitriy, Rostorguev Eduard, Kavitskiy Sergey, Novikova Inna

机构信息

National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

出版信息

J Egypt Natl Canc Inst. 2025 May 16;37(1):36. doi: 10.1186/s43046-025-00296-w.


DOI:10.1186/s43046-025-00296-w
PMID:40377745
Abstract

Glioma is a devastating type of brain tumor with high malignancy, an extremely high mortality rate, and a recurrence risk. Molecular markers are known to have a major role in classification, prognosis, survival rate, and therapy determination for different glioma subtypes. The aim of this study was to investigate the association of gliomas' main genetic markers: isocitrate dehydrogenase (IDH) mutations and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status with the survival rate in Russian patients with glioblastoma and other glial tumors. According to histological subtype, included glioma patients were divided into two groups: glioblastoma (n = 90) and other gliomas (n = 40). IDH mutations were screened by high-resolution melting-curve analysis (HRM) followed by direct sequencing, and MGMT methylation was detected with pyrosequencing. Our data showed that IDH mutations are significantly more frequent among patients with other gliomas compared to glioblastoma patients (p < 0.001). Patients with mutated IDH gene have a significantly higher progression-free survival (PFS) and overall survival (OS) rates than those with wild-type genes. MGMT promoter methylation status was found to be significantly associated with PFS, but not OS. The presence of IDH mutation with a methylated MGMT promoter significantly increased patients' PFS and OS. To our knowledge, this is the first study to investigate the association of IDH and MGMT genetic biomarkers with glioma in the Russian population. Our findings could be used in future studies to improve glioma prognosis and classification and reach a personalized treatment protocols depending on multiple molecular biomarkers.

摘要

胶质瘤是一种具有高恶性、极高死亡率和复发风险的毁灭性脑肿瘤类型。已知分子标志物在不同胶质瘤亚型的分类、预后、生存率及治疗决策中起主要作用。本研究的目的是调查俄罗斯胶质母细胞瘤和其他神经胶质瘤患者中,胶质瘤的主要遗传标志物:异柠檬酸脱氢酶(IDH)突变和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化状态与生存率之间的关联。根据组织学亚型,纳入的胶质瘤患者被分为两组:胶质母细胞瘤(n = 90)和其他胶质瘤(n = 40)。通过高分辨率熔解曲线分析(HRM)随后进行直接测序来筛选IDH突变,并用焦磷酸测序法检测MGMT甲基化。我们的数据显示,与胶质母细胞瘤患者相比,其他胶质瘤患者中IDH突变明显更常见(p < 0.001)。IDH基因突变的患者无进展生存期(PFS)和总生存期(OS)率明显高于野生型基因患者。发现MGMT启动子甲基化状态与PFS显著相关,但与OS无关。IDH突变与甲基化MGMT启动子同时存在显著提高了患者的PFS和OS。据我们所知,这是第一项在俄罗斯人群中研究IDH和MGMT基因生物标志物与胶质瘤关联的研究。我们的研究结果可用于未来的研究,以改善胶质瘤的预后和分类,并根据多种分子生物标志物制定个性化治疗方案。

相似文献

[1]
IDH mutation and MGMT methylation status in glioblastoma and other gliomas patients: a Russian retrospective cohort study.

J Egypt Natl Canc Inst. 2025-5-16

[2]
Clinical implications of TERT promoter mutation on IDH mutation and MGMT promoter methylation in diffuse gliomas.

Pathol Res Pract. 2018-6

[3]
The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

J Neurooncol. 2012-9-27

[4]
A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas.

Acta Neuropathol Commun. 2016-8-8

[5]
IDH mutation and MGMT promoter methylation in glioblastoma: results of a prospective registry.

Oncotarget. 2015-12-1

[6]
Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients.

World J Surg Oncol. 2013-10-25

[7]
Isocitrate Dehydrogenase Mutations are Better Prognostic Marker than O6-methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastomas - a Retrospective, Single-centre Molecular Genetics Study of Gliomas.

Klin Onkol. 2017

[8]
The association between C-methionine uptake, IDH gene mutation, and MGMT promoter methylation in patients with grade II and III gliomas.

Clin Radiol. 2020-8

[9]
Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation.

Asian Pac J Cancer Prev. 2014

[10]
Arterial spin labeling perfusion-weighted imaging aids in prediction of molecular biomarkers and survival in glioblastomas.

Eur Radiol. 2019-8-29

本文引用的文献

[1]
Mutant IDH in Gliomas: Role in Cancer and Treatment Options.

Cancers (Basel). 2023-5-23

[2]
Glioblastoma and Other Primary Brain Malignancies in Adults: A Review.

JAMA. 2023-2-21

[3]
Latest updates on cellular and molecular biomarkers of gliomas.

Front Oncol. 2022-11-8

[4]
Isocitrate Dehydrogenase and Mutations in Human Cancer: Prognostic Implications for Gliomas.

Br J Biomed Sci. 2022

[5]
Prognostic and predictive impact of MGMT promoter methylation status in high risk grade II glioma.

J Neurooncol. 2022-3

[6]
Prognostic and Predictive Biomarkers in Gliomas.

Int J Mol Sci. 2021-9-26

[7]
Mutations in Glioma: Double-Edged Sword in Clinical Applications?

Biomedicines. 2021-7-10

[8]
The 2021 WHO Classification of Tumors of the Central Nervous System: a summary.

Neuro Oncol. 2021-8-2

[9]
Estimation of the occurrence rates of and mutations in gliomas and the reconsideration of -wildtype anaplastic astrocytomas: an institutional experience.

J Int Med Res. 2021-6

[10]
Methylation of MGMT promoter does not predict response to temozolomide in patients with glioblastoma in Donostia Hospital.

Sci Rep. 2020-10-28

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