【摘要】：研究目的：在膠質(zhì)母細(xì)胞瘤中已發(fā)現(xiàn)核因子κB（NF-κB）的過(guò)度激活，且與膠質(zhì)母細(xì)胞瘤的發(fā)生、發(fā)展和浸潤(rùn)、復(fù)發(fā)、放射敏感性、化療耐受以及膠質(zhì)瘤細(xì)胞的免疫應(yīng)答、凋亡等生物學(xué)行為關(guān)系密切，NF-κB的功能有賴于它的活化以及它所引起的相應(yīng)基因的轉(zhuǎn)錄、表達(dá)。NF-κB抑制因子α（NFKBIA）能抑制NF-κB激活，從而抑制NF-κB在腫瘤中的生物學(xué)功能，在多種腫瘤中已發(fā)現(xiàn)NFKBIA的變異、多態(tài)性、單體型的這些轉(zhuǎn)變導(dǎo)致NFKBIA蛋白喪失抑制NF-κB蛋白活化的能力，從而阻止腫瘤細(xì)胞凋亡。然而，尚未發(fā)現(xiàn)有膠質(zhì)母細(xì)胞瘤中NFKBIA蛋白表達(dá)水平與基因型關(guān)系的報(bào)道，而膠質(zhì)母細(xì)胞瘤中NFKBIA多態(tài)性仍未知。因此我們的研究目的為研究NFKBIA在膠質(zhì)瘤中的多態(tài)性及是否存在基因型與蛋白表達(dá)、拷貝數(shù)的關(guān)系。為進(jìn)一步闡明NFKBIA在膠質(zhì)母細(xì)胞疾病發(fā)展中的作用、NFKKBIA多態(tài)性與預(yù)后關(guān)系以及針對(duì)NFKBIA穩(wěn)定性的靶向治療可能性奠定基礎(chǔ)。 研究方法：收集蘇州大學(xué)附屬第一醫(yī)院自2009年到2011年收治的膠質(zhì)瘤病人的組織標(biāo)本，選取其中病理診斷為原發(fā)多形性膠質(zhì)母細(xì)胞瘤、臨床資料較完善的24例膠質(zhì)母細(xì)胞瘤組織標(biāo)本，首先，，應(yīng)用PCR擴(kuò)增及直接測(cè)序檢測(cè)NFKBIA變異，再次，應(yīng)用Western Blot檢測(cè)NFKBIA蛋白表達(dá)，再進(jìn)一步應(yīng)用其實(shí)時(shí)定量PCR檢測(cè)NFKBIA拷貝數(shù)變異及mRNA表達(dá)。 結(jié)果：膠質(zhì)母細(xì)胞瘤中存在NFKIBA基因單核苷酸多態(tài)性rs1957106（CC/CT/TT）；包括基因型CC、基因型CT、基因型TT三種形態(tài)。膠質(zhì)母細(xì)胞瘤中NFKBIA蛋白水平在CT基因型和TT基因型中顯著低于CC基因型；膠質(zhì)母細(xì)胞瘤中NFKBIA蛋白水平和NFKBIA mRNA表達(dá)水平均顯著低于非瘤組織；而且含有CT基因型和TT基因型的膠質(zhì)母細(xì)胞瘤NFKBIA mRNA表達(dá)水平明顯低于含有CC基因型的膠質(zhì)母細(xì)胞瘤(CT和TT:0.31±0.11，CC:0.54±0.18，非瘤腦組織:0.78±0.12，P0.001)；含有CT基因型或TT基因型的10個(gè)膠質(zhì)母細(xì)胞瘤中有7個(gè)的拷貝數(shù)顯著低于含有CC基因型的腫瘤，而這些膠質(zhì)母細(xì)胞瘤同時(shí)有低NFKBIA蛋白及低NFKBIA mRNA表達(dá)水平。 結(jié)論：膠質(zhì)母細(xì)胞瘤中NFKBIA單核苷酸多態(tài)性rs1957106基因型CT、基因型TT與膠質(zhì)母細(xì)胞瘤中NFKBIA低蛋白表達(dá)、低拷貝數(shù)密切相關(guān)。
[Abstract]:Mutations, polymorphisms and haplotypes of NFKBIA have been found in a variety of tumors, resulting in the loss of the ability of NFKBIA protein to inhibit the activation of NF- 魏 B protein, thus preventing tumor cell apoptosis. In order to further elucidate the role of NFKBIA in the development of glioblastoma disease, the relationship between NFKKBIA polymorphism and prognosis and the possibility of targeted therapy for the stability of NFKBIA can be established. In 24 cases of glioblastoma with perfect clinical data, NFKBIA mutation was detected by PCR amplification and direct sequencing, and NFKBIA protein expression was detected by Western Blot. Results: single nucleotide polymorphism rs1957106 (CC/CT/TT) of NFKIBA gene was found in glioblastoma, including CC, genotype CT, genotype TT. The level of NFKBIA protein in glioblastoma was significantly lower than that in CT genotype and TT genotype, and the level of NFKBIA protein and NFKBIA mRNA expression in glioblastoma was significantly lower than that in non-tumor tissue. Conclusion: NFKBIA single nucleotide polymorphism rs1957106 genotype CT, genotype TT in glioblastoma is closely related to the low protein expression and low copy number of NFKBIA in glioblastoma.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.41

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 劉曉健;楊文濤;周曉燕;陸洪芬;施達(dá)仁;;霍奇金淋巴瘤中ΙκΒα基因突變的研究[J];臨床與實(shí)驗(yàn)病理學(xué)雜志;2010年02期

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