本文選題：膠質(zhì)瘤 + MGMT��； 參考：《濟(jì)南大學(xué)》2014年碩士論文

【摘要】：背景：腦膠質(zhì)瘤是顱內(nèi)最常見的也是最棘手的難治性腫瘤，約占顱內(nèi)腫瘤的50-60%，腦膠質(zhì)瘤生長方式為彌漫浸潤性,且與周圍正常腦組織無明顯界線，手術(shù)難以全切腫瘤,目前膠質(zhì)瘤的治療方法以手術(shù)切除，輔以放療及化療等綜合治療,但膠質(zhì)瘤易復(fù)發(fā)，因此預(yù)后較差,平均生存期較短，如何改善和提高患者的生存期,控制腫瘤的復(fù)發(fā)，一直都是研究的重點(diǎn)及難點(diǎn)。目前腫瘤的診斷有分子生物學(xué)診斷，腫瘤的治療也越來越傾向于個(gè)體化治療，O6-甲基鳥嘌呤-DNA甲基轉(zhuǎn)移酶在膠質(zhì)瘤中的表達(dá)與腫瘤的耐藥性有關(guān)，且MGMT啟動子甲基化狀態(tài)是決定MGMT在膠質(zhì)瘤中表達(dá)的主要因素,并有可能影響病人的預(yù)后，因此在膠質(zhì)瘤的治療中，以前單純根據(jù)腫瘤的病理級別決定治療方案已不再可取，如何聯(lián)合腫瘤的病理分級及腫瘤的分子生物學(xué)之間的關(guān)系成為治療膠質(zhì)瘤的一種新的方法。 目的：本研究通過免疫組織化學(xué)方法（Immunohistochemistry,IHC)，檢測MGMT在膠質(zhì)瘤中的表達(dá)，通過甲基化特異性PCR (methylation specificPCR, MSP)方法,檢測膠質(zhì)瘤中MGMT啟動子甲基化的情況，本研究旨在探討O6-甲基鳥嘌呤-DNA-甲基轉(zhuǎn)移酶(MGMT)及其甲基化的關(guān)系,及與膠質(zhì)瘤病理級別的關(guān)系。 方法：研究對象為不同級別的腦膠質(zhì)瘤石蠟標(biāo)本共42例，檢測MGMT及其甲基化在不同級別膠質(zhì)瘤中的表達(dá)情況，分析MGMT及其甲基化與膠質(zhì)瘤不同病理級別的相關(guān)性。MGMT蛋白與MGMT啟動子甲基化之間的相關(guān)性。采用SPSS16.0計(jì)算機(jī)醫(yī)學(xué)統(tǒng)計(jì)分析軟件進(jìn)行數(shù)據(jù)分析。結(jié)果：1.在42例膠質(zhì)瘤患者的腫瘤標(biāo)本中,MGMT陽性表達(dá)為24例,陽性的總體表達(dá)率為:57.14%,在不同病理級別下表達(dá)率不同,Ⅰ級膠質(zhì)瘤中陽性率為:44.44%,Ⅱ級膠質(zhì)瘤中陽性率為:54.54%,Ⅲ級膠質(zhì)瘤中陽性率為:55.55%,Ⅳ級膠質(zhì)瘤中陽性率為:69.23%.MGMT蛋白的表達(dá)率隨著腫瘤的病理級別升高而有升高的趨勢,但統(tǒng)計(jì)學(xué)分析不同病理級別的膠質(zhì)瘤之間的差異,無統(tǒng)計(jì)學(xué)意義(P0.05). 2.在42例膠質(zhì)瘤患者的腫瘤標(biāo)本中,MGMT啟動子甲基化為21例,甲基化的總體表達(dá)率為:50%,在不同病理級別下表達(dá)率不同,Ⅰ級膠質(zhì)瘤中MGMT啟動子甲基化率為:77.78%,Ⅱ級級膠質(zhì)瘤中MGMT啟動子甲基化率為:72.72%,Ⅲ級膠質(zhì)瘤中MGMT啟動子甲基化率為:33.33%,Ⅳ級膠質(zhì)瘤中MGMT啟動子甲基化率為:23.1%.統(tǒng)計(jì)學(xué)分析不同病理級別的膠質(zhì)瘤之間的MGMT啟動子甲基化率的差異有統(tǒng)計(jì)學(xué)意義(P0.05). 3.在42例膠質(zhì)瘤患者的腫瘤標(biāo)本中，24例MGMT蛋白表達(dá)陽性的膠質(zhì)瘤組織中，8例膠質(zhì)瘤組織中MGMT基因啟動子甲基化，陽性率為33.33%，24例MGMT蛋白表達(dá)陰性的膠質(zhì)瘤組織中，13例膠質(zhì)瘤組織中MGMT基因啟動子甲基化，陽性率為72.22%，用Spearman相關(guān)系數(shù)分析：P0.05. 4.42例膠質(zhì)瘤患者的腫瘤標(biāo)本中，MGMT蛋白表達(dá)與患者的年齡及性別無關(guān)系。 結(jié)論:1.不同病理級別的膠質(zhì)瘤MGMT蛋白的陽性表達(dá)率不同，，MGMT蛋白的陽性表達(dá)率隨著膠質(zhì)瘤的病理級別的增高有上升的趨勢，但是統(tǒng)計(jì)學(xué)分析差異無統(tǒng)計(jì)學(xué)意義，因此MGMT蛋白的表達(dá)與膠質(zhì)瘤的病理級別無相關(guān)性。 2.不同病理級別的膠質(zhì)瘤MGMT基因啟動子甲基化率不同，統(tǒng)計(jì)學(xué)分析差異有統(tǒng)計(jì)學(xué)意義，因此MGMT基因啟動子甲基化率與膠質(zhì)瘤的病理級別呈負(fù)相關(guān)性。 3.腦膠質(zhì)瘤中，MGMT蛋白的表達(dá)與MGMT基因啟動子甲基化呈負(fù)相關(guān)，經(jīng)統(tǒng)計(jì)學(xué)檢驗(yàn)差異有統(tǒng)計(jì)學(xué)意義。 4.腦膠質(zhì)瘤中MGMT蛋白的表達(dá)與患者的年齡及性別無關(guān)，因此在臨床為患者制定個(gè)體化的治療方案時(shí)，性別，年齡不能作為考慮因素。
[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.

【學(xué)位授予單位】：濟(jì)南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R739.41

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