Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
Cancer Gene Ther. 2017 May;24(5):215-220. doi: 10.1038/cgt.2017.7. Epub 2017 Apr 14.
This study aims to investigate the associations of O-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.
本研究旨在探讨 O-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）基因多态性（Leu84Phe 和 Ile143Val）与替莫唑胺（TMZ）耐药及恶性脑胶质瘤患者预后的关系。共纳入 212 例经病理证实的恶性脑胶质瘤患者作为病例组。所有患者均口服 TMZ，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（稳定期+进展期）。采用聚合酶链反应-限制性片段长度多态性分析技术检测 Leu84Phe 和 Ile143Val 基因多态性。通过随访获得所有患者的生存时间和生存结局。TMZ 敏感组和 TMZ 耐药组患者 Leu84Phe 基因型和等位基因分布差异有统计学意义。MGMT 基因 Leu84Phe 的 CT、TT 和 CT+TT 基因型及 T 等位基因可能与恶性脑胶质瘤患者 TMZ 耐药性增加有关。Logistic 回归分析显示，MGMT 基因 Leu84Phe 和病理分级是恶性脑胶质瘤患者 TMZ 耐药增加的独立危险因素。Kaplan-Meier 生存曲线显示，两组 Leu84Phe 基因型 CT+TT 和 CC 的患者平均生存时间差异有统计学意义。COX 回归分析显示，Leu84Phe、肿瘤切除程度和病理分级是恶性脑胶质瘤患者的独立预后因素。本研究表明，MGMT 基因 Leu84Phe 可能是恶性脑胶质瘤患者 TMZ 耐药和预后不良的危险因素。
