文章：

MGMT基因多态性与替莫唑胺耐药性和恶性胶质瘤患者预后的相关性：一项基于中国人群的研究

Correlations of MGMT genetic polymorphisms with temozolomide resistance and prognosis of patients with malignant gliomas: a population-based study in China

原文发布日期：2017-04-14 

英文摘要：

This study aims to investigate the associations of O6-methylguanine-DNA methyltransferase (MGMT) genetic polymorphisms (Leu84Phe and Ile143Val) with temozolomide (TMZ) resistance and prognosis of patients with malignant gliomas. A total of 212 patients diagnosed with malignant gliomas were enrolled in this study as the case group. All of these patients took oral TMZ and were assigned into the TMZ-sensitive (complete response+partial response) and the TMZ-resistant (stable disease+progressive disease) groups based on the clinical response after chemotherapy. The polymerase chain reaction-restriction fragment length polymorphism was used to identify the gene polymorphism of Leu84Phe and Ile143Val. The survival time and survival outcomes of all the patients were obtained by follow-up. There were significant differences in the genotype and allele of Leu84Phe between the TMZ-sensitive and the TMZ-resistant groups. The CT, TT and CT+TT genotypes and the T allele of MGMT gene Leu84Phe may be associated with increasing TMZ resistance in patients with malignant gliomas. Logistic regression analysis showed that Leu84Phe of MGMT gene and pathological grade were independent risk factors for the increase of TMZ resistance in patients with malignant gliomas. Kaplan–Meier survival curve revealed that the average survival time of patients with the CT+TT and CC genotypes of Leu84Phe in the two groups was statistically significant. COX regression analysis showed that Leu84Phe, degree of resection and pathological grade were independent prognostic factors for patients with malignant gliomas. Our study demonstrates that Leu84Phe of MGMT gene might be a risk factor of TMZ resistance and poor prognosis of patients with malignant gliomas. 

摘要翻译： 

本研究旨在探讨O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因多态性（Leu84Phe和Ile143Val）与恶性胶质瘤患者替莫唑胺（TMZ）耐药性及预后的关联。研究共纳入212例经病理确诊的恶性胶质瘤患者作为病例组，所有患者均口服TMZ化疗，并根据化疗后临床疗效分为TMZ敏感组（完全缓解+部分缓解）和TMZ耐药组（疾病稳定+疾病进展）。采用聚合酶链反应-限制性片段长度多态性技术检测Leu84Phe和Ile143Val位点的基因多态性，通过随访获取患者生存时间和生存结局。结果显示：TMZ敏感组与耐药组在Leu84Phe位点的基因型和等位基因分布存在显著差异，MGMT基因Leu84Phe位点的CT、TT及CT+TT基因型与T等位基因可能增加恶性胶质瘤患者的TMZ耐药风险。Logistic回归分析表明MGMT基因Leu84Phe多态性和病理分级是TMZ耐药性增加的独立危险因素。Kaplan-Meier生存曲线显示两组中携带CT+TT基因型与CC基因型患者的平均生存时间存在统计学差异。COX回归分析提示Leu84Phe多态性、肿瘤切除程度及病理分级是影响患者预后的独立因素。本研究表明MGMT基因Leu84Phe多态性可能是导致恶性胶质瘤患者TMZ耐药和不良预后的风险因素。

原文链接：

Correlations of MGMT genetic polymorphisms with temozolomide resistance and prognosis of patients with malignant gliomas: a population-based study in China