CAJ | 학술논문

目的探讨恶性脑胶质瘤组织O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)基因启动子甲基化状态及MGMT蛋白表达与患者生存预后的关系,评价MS-MLPA技术检测MGMT基因启动子甲基化状态对脑胶质瘤化疗的意义. 方法选择自2006至2010年南方医科大学珠江医院神经外科手术治疗且病理证实为恶性脑胶质瘤(WHOⅢ级、Ⅳ级)的39例患者为研究对象,应用免疫组化染色法检测肿瘤组织MGMT蛋白表达,应用MS-MLPA技术检测MGMT基因启动子甲基化状态,并观察患者化疗后总生存时间. 结果肿瘤组织中MGMT蛋白表达阳性、弱阳性者与表达阴性者生存时间比较差异有统计学意义(P=0.003),MGMT蛋白表达阳性者比表达阴性者预后更差.肿瘤组织中MGMT基因启动子未甲基化者、低度过甲基化者、中度过甲基化者、高度过甲基化者生存时间两两比较差异均有统计学意义(P＜0.05),MGMT基因启动子过甲基化率越高者预后越好.MGMT蛋白表达与MGMT基因启动子甲基化状态存在统计学相关性(r=0.697,P=0.000),基因甲基化程度越高者蛋白表达越低. 结论 MGMT蛋白表达与MGMT基因启动子甲基化状态均可以作为接受烷化剂化疗的恶性胶质瘤患者生存期的预测指标.MS-MLPA技术是一种可靠的检测MGMT基因启动子甲基化状态的方法.
목적 탐토악성뇌효질류조직O6-갑기조표령-DNA-갑기전이매(MGMT)기인계동자갑기화상태급MGMT단백표체여환자생존예후적관계,평개MS-MLPA기술검측MGMT기인계동자갑기화상태대뇌효질류화료적의의. 방법 선택자2006지2010년남방의과대학주강의원신경외과수술치료차병리증실위악성뇌효질류(WHOⅢ급、Ⅳ급)적39례환자위연구대상,응용면역조화염색법검측종류조직MGMT단백표체,응용MS-MLPA기술검측MGMT기인계동자갑기화상태,병관찰환자화료후총생존시간. 결과 종류조직중MGMT단백표체양성、약양성자여표체음성자생존시간비교차이유통계학의의(P=0.003),MGMT단백표체양성자비표체음성자예후경차.종류조직중MGMT기인계동자미갑기화자、저도과갑기화자、중도과갑기화자、고도과갑기화자생존시간량량비교차이균유통계학의의(P＜0.05),MGMT기인계동자과갑기화솔월고자예후월호.MGMT단백표체여MGMT기인계동자갑기화상태존재통계학상관성(r=0.697,P=0.000),기인갑기화정도월고자단백표체월저. 결론 MGMT단백표체여MGMT기인계동자갑기화상태균가이작위접수완화제화료적악성효질류환자생존기적예측지표.MS-MLPA기술시일충가고적검측MGMT기인계동자갑기화상태적방법.
Objective To study the correlations between O (6) -methylguanine-DNA-methyltransferase (MGMT) gene promoter methylation status in malignant glioma tissues and both MGMT protein expression and survival prognosis in these patients, and evaluate the significance of MGMT gene methylation status analyzing with methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method in chemotherapy of brain glioma.Methods Thirty-nine patients with gliomas confirmed by pathology (WHO grade Ⅲ and grade Ⅳ)were collected in our study; the patient's overall survival (OS) after chemotherapy was tracked.MGMT protein expression of glioma tissues was detected by immunohistochemical staining,and MGMT promoter methylation status was detected by MS-MLPA method. Results Statistical difference of OS time was noted between patients with MGMT-negative and patients with MGMT-positive/-weak-positive (P=0.003).The prognosis in patients with positive MGMT protein expression was obviously poorer than that in patients with negative expression. In the groups of MGMT promoter un-methylation, mild hypermethylation, moderate hypermethylation and extensive hypermethylation, significant statistical difference of OS time was noted between each 2 groups (P＜0.05); the higher degree of methylation,the better prognosis. Statistical correlation was noted between MGMT protein expression and promoter methylation status (r=0.697,P=0.000); the higher degree ofmethylation,the lower protein exression of MGMT. Conclusion Both MGMT protein expression and promoter methylation status can be regarded as prognostic indicator of OS in patients with malignant glioma accepted alkylating agent chemotherapy; MS-MLPA is a reliable method to detect MGMT gene promoter methylation status.