【摘要】：研究背景 腦膠質(zhì)瘤是最常見的中樞神經(jīng)系統(tǒng)腫瘤之一,在中樞神經(jīng)系統(tǒng)腫瘤中發(fā)病率僅次于腦膜瘤,位于第二位。隨著現(xiàn)代醫(yī)學(xué)對疾病認(rèn)識水平的提高及CT、MR等先進(jìn)檢驗(yàn)技術(shù)的推廣應(yīng)用,膠質(zhì)瘤的年發(fā)病率持續(xù)升高。膠質(zhì)瘤具有高度增殖能力和侵襲性,是神經(jīng)外科常見的致死性疾病之一。由于膠質(zhì)瘤細(xì)胞的高度侵襲性,術(shù)中膠質(zhì)瘤邊界不清,手術(shù)全切難度大,臨床預(yù)后不佳且復(fù)發(fā)率較高。 近年來,對于基于分子生物學(xué)的腫瘤診斷標(biāo)志物及基因靶向治療越來越受到重視。高遷移率蛋白A2(High mobility group protein A2,HMGA2)是一種調(diào)控基因轉(zhuǎn)錄的結(jié)構(gòu)性轉(zhuǎn)錄因子,被發(fā)現(xiàn)在許多良惡性腫瘤的發(fā)生、增殖及轉(zhuǎn)移過程中起重要作用,現(xiàn)被認(rèn)為是潛在的診斷標(biāo)志物和基因靶向治療藥物。 目的 探討HMGA2和基質(zhì)金屬蛋白酶9(Matrix metalloproteinase9,MMP-9)在腦膠質(zhì)瘤細(xì)胞中的表達(dá)及其與臨床病理分型和侵襲性的關(guān)系。 材料與方法 收集了2012年2月至2012年10月在山東大學(xué)附屬省立醫(yī)院神經(jīng)外科行手術(shù)切除保存完好的腦膠質(zhì)細(xì)胞瘤標(biāo)本57例,其中男性27例,女性30例。其中低度惡性(Ⅱ級)標(biāo)本、中度惡性(Ⅲ級)、高度惡性(Ⅳ級)標(biāo)本分別為23、18和16例。6例對照組標(biāo)本取自腦外傷手術(shù)患者的正常腦組織。 采用免疫組化(S-P)方法檢測HMGA2、MMP-9在不同級別腦膠質(zhì)瘤標(biāo)本中的表達(dá)情況。采用實(shí)時熒光定量聚合酶鏈反應(yīng)(RT-PCR)方法測量HMGA2、MMP-9的mRNA在不同級別腦膠質(zhì)瘤標(biāo)本中的表達(dá)情況。并選擇合適統(tǒng)計(jì)學(xué)方法對所得的結(jié)果進(jìn)行分析,最終得出HMGA2、MMP-9之間的相關(guān)關(guān)系及其與腫瘤病理級別間的相關(guān)關(guān)系的結(jié)論。 結(jié)果 免疫組化結(jié)果顯示,HMGA2在惡性膠質(zhì)瘤細(xì)胞核表達(dá)率為91.2%(52/57),其中高表達(dá)(+++)29.8%(17/57)、中表達(dá)(++)47.4%(27/57)、低表達(dá)或陰性(+或0)22.8%(13/57),在正常腦組織細(xì)胞未見表達(dá)。且HMGA2在膠質(zhì)母細(xì)胞瘤(P=0.033)與間變性星形細(xì)胞瘤(P=0.011)中的表達(dá)顯著性高于星形細(xì)胞瘤,而在膠質(zhì)母細(xì)胞瘤與間變性星形細(xì)胞瘤中的表達(dá)之間無顯著性差異(P=0.923)。HMGA2表達(dá)與MMP-9(P＜0.01)、Ki-67(P＜0.01)顯著性正相關(guān)。RT-PCR結(jié)果顯示HMGA2在轉(zhuǎn)錄水平上與MMP-9(r=0.441,P=0.027)和Ki-67(r=0.498,P=0.011)表達(dá)顯著性正相關(guān)。 結(jié)論 HMGA2的表達(dá)與代表腫瘤增值能力的Ki-67和細(xì)胞侵襲能力的MMP-9的表達(dá)呈顯著性正相關(guān)關(guān)系。提示HMGA2的過表達(dá)可能增強(qiáng)了腦膠質(zhì)瘤細(xì)胞的增殖及侵襲能力,可以作為腦膠質(zhì)瘤的腫瘤診斷標(biāo)志物和基因靶向治療藥物做進(jìn)一步研究。
[Abstract]:Background glioma is one of the most common tumors in the central nervous system. With the development of modern medicine and the application of advanced detection techniques such as CTN Mr, the annual incidence of glioma is increasing. Glioma has high proliferative ability and invasiveness and is one of the common fatal diseases in neurosurgery. Because of the high invasiveness of glioma cells, the boundary of glioma is not clear, the operation is difficult, the clinical prognosis is poor and the recurrence rate is high. In recent years, more and more attention has been paid to tumor diagnostic markers and gene targeting therapy based on molecular biology. High mobility protein A2 (High mobility group protein A2HMGA2 is a structural transcription factor that regulates gene transcription and has been found to play an important role in the occurrence, proliferation and metastasis of many benign and malignant tumors. It is considered to be a potential diagnostic marker and gene-targeted therapy drug. Objective to investigate the expression of HMGA2 and Matrix metalloproteinase 9 (Matrix metalloproteinase 9) in glioma cells and their relationship with clinicopathological classification and invasion. Materials and methods from February 2012 to October 2012, 57 cases of well-preserved brain glioma, including 27 males and 30 females, were collected from neurosurgery department of affiliated provincial hospital of Shandong University. The specimens of low grade (grade 鈪，

本文編號：2169079