脑脊液<i>MGMT</i>启动子甲基化在胶质瘤诊断中的应用

王龙; 黄彩菲; 葛剑; 陈治标; 蔡强; 刘宝辉; 陈谦学

doi:10.3971/j.issn.1000-8578.2018.18.0126

脑脊液MGMT启动子甲基化在胶质瘤诊断中的应用

Application of MGMT Promoter Methylation of Cerebrospinal Fluid in Diagnosis of Glioma

摘要

摘要:
目的比较胶质瘤患者脑脊液与外周血中MGMT（O⁶-甲基鸟嘌呤-DNA-甲基转移酶）启动子甲基化在胶质瘤初期诊断中的敏感度和特异性。
方法收集283例胶质瘤患者肿瘤组织及其对应的术前外周血和脑脊液，10例颅脑外伤患者挫伤的脑组织及其对应的术前外周血、脑脊液。MGMT启动子甲基化状态通过甲基化特异性PCR（methylation-specific PCR, MSP）确定，比较脑肿瘤组织，外周血和脑脊液中MGMT启动子甲基化率。
结果不同级别胶质瘤组织MGMT启动子甲基化阳性率分别为68.13%（WHO Ⅱ）、65.69%（WHO Ⅲ）以及67.78%（WHO Ⅳ），三者之间差异无统计学意义（P > 0.05）。胶质瘤瘤体组织、对应的外周血和脑脊液启动子甲基化率为分别为67.14%、44.87%和66.08%，阴性对照组中检测结果均为0。MGMT启动子甲基化阳性瘤体组织，对应的脑脊液中MGMT启动子甲基化敏感度为79.66%（141/177），较对应的外周血58.82%（110/187）高（P < 0.05）。
结论术前患者肿瘤组织、脑脊液和外周血中MGMT启动子甲基化率与肿瘤级别无关。与外周血相比，脑脊液中的MGMT启动子甲基化特异性和敏感度更高。

Abstract:
Objective To compare the sensitivity and specificity of O⁶-methylguanine-DNA methyltransferase(MGMT) promoter methylation between peripheral blood and cerebrospinal fluid in the initial diagnosis of glioma patients.
Methods We collected the tumor tissues, preoperative blood plasma and cerebrospinal fluid from 283 patients with glioma admitted by neurosurgery. Contused brain tissues of 10 patients with craniocerebral trauma, and the corresponding blood plasma and cerebrospinal fluid were collected for the negative control. Methylation status of MGMT promoter was determined by methylation-specific PCR(MSP). The methylation rate of MGMT promoter was compared among tumor tissues, preoperative blood plasma and cerebrospinal fluid.
Results The methylation rates of glioma tissues, the corresponding peripheral blood and cerebrospinal fluid promoters were 67.14%, 44.87% and 66.08%, respectively, and 0 in the negative control group. The positive rates of MGMT promoter methylation in different grades of gliomas were 68.13% (WHO Ⅱ), 65.69% (WHO Ⅲ) and 67.78% (WHO Ⅳ), respectively (P > 0.05). In the glioma tissues with positive MGMT promoter methylation, the sensitivity of MGMT promoter methylation in cerebrospinal fluid was 79.66% (141/177), higher than that in blood plasma (58.82%(110/187)) (P < 0.05).
Conclusion The methylation rates of MGMT promoter in tumor tissues, cerebrospinal fluid and peripheral blood are independent of tumor grade. Compared with peripheral blood, the methylation of MGMT promoter in cerebrospinal fluid is more specific and sensitive.

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