本文關(guān)鍵詞： 腦膠質(zhì)瘤 SOCS3基因甲基化 IDH1基因突變 分子標(biāo)志物 焦磷酸測(cè)序　出處：《西北大學(xué)》2015年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：腦膠質(zhì)瘤在腦腫瘤中出現(xiàn)的頻率最高,具有病程進(jìn)展快,難治愈,患者的存活期短等特征。近年來(lái),腦膠質(zhì)瘤的治療引入了分子標(biāo)志物的概念,分子標(biāo)志物的應(yīng)用能幫助腦膠質(zhì)瘤的臨床診斷和愈后的預(yù)測(cè),彌補(bǔ)了傳統(tǒng)的病理學(xué)分級(jí)和分型不能判斷臨床預(yù)后的不足。在腫瘤基因組學(xué)和腫瘤分子遺傳學(xué)的基礎(chǔ)上,衍生出了病理分子分型的概念,其能鑒別和診斷傳統(tǒng)方法難以區(qū)分的混合型腫瘤。因此,對(duì)腦膠質(zhì)瘤診療和預(yù)后相關(guān)的分子標(biāo)志物的篩選,對(duì)其臨床治療具有重要意義。SOCS3是JAK-STAT信號(hào)通路的一個(gè)關(guān)鍵負(fù)調(diào)控因子,被認(rèn)為是一個(gè)腫瘤抑制基因。有研究表明,SOCS3啟動(dòng)子甲基化程度在病理學(xué)分級(jí)和類(lèi)型不同的腦膠質(zhì)瘤中不同,WHO Ⅳ級(jí)腦膠質(zhì)瘤中SOCS3甲基化程度低于WHOⅡ、Ⅲ級(jí)的腦膠質(zhì)瘤,膠質(zhì)母細(xì)胞瘤中SOCS3啟動(dòng)子的甲基化水平較其它類(lèi)型中要低。而且SOCS3啟動(dòng)子甲基化程度不相同的病人,其預(yù)后也有差異。本文在找到了能代表SOCS3的啟動(dòng)子區(qū)甲基化程度的5個(gè)CpG位點(diǎn),并檢測(cè)了其甲基化水平,可作為一個(gè)分子標(biāo)志。本課題用焦磷酸測(cè)序法檢測(cè)了51例不同級(jí)別和類(lèi)型的腦膠質(zhì)瘤的SOCS3啟動(dòng)子的甲基化和IDH1 R132H的突變情況,并用實(shí)時(shí)定量反轉(zhuǎn)錄PCR(qRT-PCR)法對(duì)SOCS3在mHMA水平的表達(dá)進(jìn)行了檢測(cè)。結(jié)果表明,WHOⅣ級(jí)中SOCS3啟動(dòng)子甲基化程度比WHOⅢ級(jí)低,且在膠質(zhì)母細(xì)胞瘤組中SOCS3啟動(dòng)子的甲基化程度比少突星形細(xì)胞瘤組中的低。經(jīng)過(guò)數(shù)據(jù)分析,我們得出SOCS3啟動(dòng)子高甲基化組的臨床樣本在mRNA水平的表達(dá)量比非甲基化組的低的結(jié)論。經(jīng)過(guò)綜合數(shù)據(jù)分析,我們首次發(fā)現(xiàn)了IDH1的突變可導(dǎo)致SOCS3啟動(dòng)子甲基化的顯著升高。最后我們得出,SOCS3在某種程度上可作為腦膠質(zhì)瘤分級(jí)、分型和預(yù)后的一個(gè)潛在分子標(biāo)志物,不過(guò)還需要大量充分的數(shù)據(jù)來(lái)支持。我們的工作給SOCS3作為分子標(biāo)志物的研究提供了一定的證據(jù)和數(shù)據(jù)基礎(chǔ)。
[Abstract]:Gliomas have the highest frequency of occurrence in brain tumors, with the characteristics of rapid progression, difficult to cure and short survival period. In recent years, the treatment of gliomas has introduced the concept of molecular markers. The application of molecular markers can help the clinical diagnosis and prognosis of glioma, and make up for the deficiency of traditional pathological classification and classification, which can not judge the clinical prognosis. The concept of pathological molecular typing is derived, which can differentiate and diagnose mixed tumors which are difficult to distinguish between traditional methods. Therefore, the screening of molecular markers related to the diagnosis, treatment and prognosis of gliomas, SOCS3 is a key negative regulator of JAK-STAT signaling pathway. It has been shown that the degree of methylation of SOCS3 promoter in gliomas of different grade and type of pathology is lower than that of gliomas of grade WHO 鈪，

本文編號(hào)：1529744