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在一个中国汉族胶质瘤队列中,rs16906252:C>T单核苷酸多态性与总生存期延长或替莫唑胺反应无关。

The rs16906252:C>T SNP is not associated with increased overall survival or temozolomide response in a Han-Chinese glioma cohort.

作者信息

Wei Kuo-Chen, Chen Chia-Yuan, Feng Li-Ying, Huang Wei-Tzu, Chen Chia-Hua, Hsu Peng-Wei, Wang Kai, Hood Leroy E, Chen Leslie Y

机构信息

Department of Neurosurgery, Chang Gung Memorial Hospital-Linkou Medical Center, Taoyuan, Taiwan, Republic of China.

College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.

出版信息

PLoS One. 2017 Jun 2;12(6):e0178842. doi: 10.1371/journal.pone.0178842. eCollection 2017.

Abstract

The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction endonuclease digestion. Contrary to the previous findings, we found no association between rs16906252 genotypes and promoter methylation on MGMT. The lower-grade glioma (LGGs) patients carrying the C allele with rs16906252 showed a surprisingly better OST (P = 0.04). Furthermore, the LGG patients carrying hypo-methylated MGMT promoter and rs16906252 T allele showed significantly poorer prognosis. The prognostic benefit of MGMT promoter methylation and genotypes on gliomas patients is marginal. A new molecular stratified patient grouping of LGGs is potentially associated with poorer OST. Active MGMT might have a protective role in LGG tumors, enabling evolution to severe malignancy.

摘要

O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的甲基化状态与胶质瘤及其他癌症的预后相关。近期研究表明,MGMT启动子中的单核苷酸多态性(SNP)rs16906252与启动子甲基化相关,是总生存时间(OST)及替莫唑胺(TMZ)治疗反应的预测指标。然而,这些发现尚未在汉族人群中进行系统研究。我们分析了72例汉族胶质瘤患者中rs16906252多态性、MGMT甲基化状态与OST之间的相关性。MGMT启动子甲基化通过亚硫酸氢盐转化后焦磷酸测序进行检测,而rs16906252通过限制性内切酶消化进行检测。与先前的发现相反,我们发现rs16906252基因型与MGMT启动子甲基化之间无关联。携带rs16906252 C等位基因的低级别胶质瘤(LGG)患者的OST出人意料地更好(P = 0.04)。此外,携带低甲基化MGMT启动子和rs16906252 T等位基因的LGG患者预后明显较差。MGMT启动子甲基化和基因型对胶质瘤患者的预后益处不大。一种新的LGG分子分层患者分组可能与较差的OST相关。活跃的MGMT可能在LGG肿瘤中具有保护作用,促使其演变为严重恶性肿瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/992b/5456392/705c084d80ec/pone.0178842.g001.jpg

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