MGMT及其甲基化在胶质瘤的表达与病理级别的相关性研究

发布时间：2018-04-15 09:34

本文选题：胶质瘤 + MGMT　；参考：《济南大学》2014年硕士论文

【摘要】：背景：脑胶质瘤是颅内最常见的也是最棘手的难治性肿瘤，约占颅内肿瘤的50-60%，脑胶质瘤生长方式为弥漫浸润性,且与周围正常脑组织无明显界线，手术难以全切肿瘤,目前胶质瘤的治疗方法以手术切除，辅以放疗及化疗等综合治疗,但胶质瘤易复发，因此预后较差,平均生存期较短，如何改善和提高患者的生存期,控制肿瘤的复发，一直都是研究的重点及难点。目前肿瘤的诊断有分子生物学诊断，肿瘤的治疗也越来越倾向于个体化治疗，O6-甲基鸟嘌呤-DNA甲基转移酶在胶质瘤中的表达与肿瘤的耐药性有关，且MGMT启动子甲基化状态是决定MGMT在胶质瘤中表达的主要因素,并有可能影响病人的预后，因此在胶质瘤的治疗中，以前单纯根据肿瘤的病理级别决定治疗方案已不再可取，如何联合肿瘤的病理分级及肿瘤的分子生物学之间的关系成为治疗胶质瘤的一种新的方法。目的：本研究通过免疫组织化学方法（Immunohistochemistry,IHC)，检测MGMT在胶质瘤中的表达，通过甲基化特异性PCR (methylation specificPCR, MSP)方法,检测胶质瘤中MGMT启动子甲基化的情况，本研究旨在探讨O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)及其甲基化的关系,及与胶质瘤病理级别的关系。方法：研究对象为不同级别的脑胶质瘤石蜡标本共42例，检测MGMT及其甲基化在不同级别胶质瘤中的表达情况，分析MGMT及其甲基化与胶质瘤不同病理级别的相关性。MGMT蛋白与MGMT启动子甲基化之间的相关性。采用SPSS16.0计算机医学统计分析软件进行数据分析。结果：1.在42例胶质瘤患者的肿瘤标本中,MGMT阳性表达为24例,阳性的总体表达率为:57.14%,在不同病理级别下表达率不同,Ⅰ级胶质瘤中阳性率为:44.44%,Ⅱ级胶质瘤中阳性率为:54.54%,Ⅲ级胶质瘤中阳性率为:55.55%,Ⅳ级胶质瘤中阳性率为:69.23%.MGMT蛋白的表达率随着肿瘤的病理级别升高而有升高的趋势,但统计学分析不同病理级别的胶质瘤之间的差异,无统计学意义(P0.05). 2.在42例胶质瘤患者的肿瘤标本中,MGMT启动子甲基化为21例,甲基化的总体表达率为:50%,在不同病理级别下表达率不同,Ⅰ级胶质瘤中MGMT启动子甲基化率为:77.78%,Ⅱ级级胶质瘤中MGMT启动子甲基化率为:72.72%,Ⅲ级胶质瘤中MGMT启动子甲基化率为:33.33%,Ⅳ级胶质瘤中MGMT启动子甲基化率为:23.1%.统计学分析不同病理级别的胶质瘤之间的MGMT启动子甲基化率的差异有统计学意义(P0.05). 3.在42例胶质瘤患者的肿瘤标本中，24例MGMT蛋白表达阳性的胶质瘤组织中，8例胶质瘤组织中MGMT基因启动子甲基化，阳性率为33.33%，24例MGMT蛋白表达阴性的胶质瘤组织中，13例胶质瘤组织中MGMT基因启动子甲基化，阳性率为72.22%，用Spearman相关系数分析：P0.05. 4.42例胶质瘤患者的肿瘤标本中，MGMT蛋白表达与患者的年龄及性别无关系。结论:1.不同病理级别的胶质瘤MGMT蛋白的阳性表达率不同，，MGMT蛋白的阳性表达率随着胶质瘤的病理级别的增高有上升的趋势，但是统计学分析差异无统计学意义，因此MGMT蛋白的表达与胶质瘤的病理级别无相关性。 2.不同病理级别的胶质瘤MGMT基因启动子甲基化率不同，统计学分析差异有统计学意义，因此MGMT基因启动子甲基化率与胶质瘤的病理级别呈负相关性。 3.脑胶质瘤中，MGMT蛋白的表达与MGMT基因启动子甲基化呈负相关，经统计学检验差异有统计学意义。 4.脑胶质瘤中MGMT蛋白的表达与患者的年龄及性别无关，因此在临床为患者制定个体化的治疗方案时，性别，年龄不能作为考虑因素。
[Abstract]:Background: glioma is the most common and most incurable tumors, accounting for about 50-60% of intracranial tumors, brain glioma is diffuse, and no obvious boundaries with the surrounding normal brain tissue, it is difficult to total resection of the tumor, the current treatment of glioma resection, radiotherapy and chemotherapy, but the glioma recurrence, the prognosis is poor, the average survival time is short, how to improve the survival of patients, control of tumor recurrence, has always been the focus and difficulty of research. The diagnosis of cancer molecular diagnosis, treatment of tumors are increasingly inclined to individual the treatment, the drug resistance of O6- methylguanine -DNA methyltransferase expression and tumor enzyme in glioma, and MGMT promoter methylation is a major factor in determining the expression of MGMT in gliomas, and may affect the disease Therefore, in the treatment of glioma, it is no longer advisable to decide the treatment plan only according to the pathological level of tumor. How to combine the pathological grading of tumor and the molecular biology of tumor is a new way to treat glioma.
Objective: This study by immunohistochemical method (Immunohistochemistry, IHC), to detect the expression of MGMT in glioma, by methylation specific PCR (methylation specificPCR MSP) method, the detection of glioma in MGMT promoter methylation status, this study aimed to investigate the O6- methylguanine -DNA- methyltransferase (MGMT) the relationship and its methylation, and its relationship with the pathological grade of glioma.
Methods: a total of 42 cases of brain glioma specimens of different levels, to detect the expression of MGMT and methylation in different grade gliomas, the correlation between.MGMT protein and MGMT analysis of MGMT and its methylation and gliomas of different pathological grades start the correlation between promoter methylation. Using computer medical data analysis SPSS16.0 the statistical analysis software. Results: in 1. tumor specimens of 42 cases of glioma patients, the positive expression of MGMT in 24 cases, the overall expression for positive rate: 57.14%, the expression level was different in different pathological grade of glioma, the positive rate was 44.44%, the positive rate of grade II gliomas: 54.54%, the positive rate of grade III glioma was 55.55%, the positive rate of grade IV gliomas: the expression rate of 69.23%.MGMT protein with tumor pathological level increased and had a tendency to increase, but no statistical analysis with pathological level The difference between gliomas was not statistically significant (P0.05).
In 2. tumor specimens of 42 glioma patients in MGMT promoter methylation in 21 cases, the overall expression rate for methylation: 50%, expression in different pathological grades under the rate of different grade gliomas, MGMT promoter methylation rate: 77.78%, MGMT promoter methylation rate was 2 grade gliomas: 72.72%, grade III glioma MGMT promoter methylation rate was 33.33%, grade IV glioma MGMT promoter methylation rate: 23.1%. statistical analysis of promoter methylation rate start the difference between gliomas of different pathological grades of MGMT were statistically significant (P0.05).
In 3. tumor specimens of 42 cases of glioma patients, 24 cases of positive expression of MGMT protein in glioma tissues, 8 cases of MGMT in glioma gene promoter methylation, the positive rate was 33.33%, 24 cases of MGMT negative expression in glioma tissues, 13 cases of glioma MGMT gene promoter methylation analysis, the positive rate was 72.22%, with Spearman correlation coefficient: P0.05.
In 4.42 patients with glioma, the expression of MGMT protein was not related to the age and sex of the patients.
Conclusion: the positive expression of 1. different pathological grades of glioma MGMT protein was different, the positive rate of MGMT protein expression with the pathological grade of glioma was a rising trend, but the statistical analysis showed no significant difference, so the expression of MGMT protein and the pathological grade of glioma patients.
2. the methylation rate of MGMT gene promoter in different pathological grades of glioma is different. The difference between statistical analysis is statistically significant. Therefore, the promoter methylation rate of MGMT gene is negatively correlated with the pathological grade of glioma.
In 3. glioma, the expression of MGMT protein is negatively correlated with the promoter methylation of MGMT gene, and the statistical difference is statistically significant.
4., the expression of MGMT protein in glioma is not related to the age and sex of patients. Therefore, gender and age can not be considered as a consideration when making individualized treatment plan for clinical patients.

【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.41

【参考文献】