發(fā)布時(shí)間：2018-01-14 21:12

  本文關(guān)鍵詞：新疆維吾爾族宮頸癌組織中全基因組表達(dá)譜分析及與凋亡相關(guān)基因c-IAP1、Bcl-xl、Bcl2的檢測　出處：《新疆醫(yī)科大學(xué)》2014年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 凋亡 基因芯片 宮頸癌 Bcl2 Bcl-xl C-IAP1

【摘要】：目的：從基因表達(dá)譜差異的角度,利用基因芯片技術(shù)尋找維吾爾族宮頸癌與宮頸非病變組織不同的相關(guān)基因差異表達(dá)情況,并對凋亡相關(guān)基因驗(yàn)證,探討維吾爾族宮頸癌的發(fā)病機(jī)制及與臨床病理指標(biāo)的關(guān)系。方法：收集新疆維吾爾族子宮肌瘤的非病變宮頸組織及宮頸癌組織各5例用于全基因組表達(dá)譜基因芯片篩選差異表達(dá)基因,采用實(shí)時(shí)熒光定量PCR及免疫組化對45例宮頸癌,21例宮頸非病變組織中Bcl2、Bcl-x1、c-IAP1進(jìn)行檢測,并分析各分子表達(dá)水平與相應(yīng)臨床病理指標(biāo)的關(guān)系。結(jié)果：(1)采用Affymetrix的全基因組寡核苷酸基因芯片,對5對浸潤性宮頸癌標(biāo)本及宮頸非病變組織的18947個(gè)基因的表達(dá)譜差異同時(shí)進(jìn)行了研究,結(jié)果顯示：與宮頸非病變組織相比,共篩選到差異表達(dá)基因2758個(gè)其中上調(diào)基因1326個(gè),下調(diào)基因1432個(gè),分屬不同的通路,已知與腫瘤凋亡發(fā)生相關(guān)的基因10個(gè),表達(dá)上調(diào)的的基因中7個(gè)屬于凋亡相關(guān)通路基因。凋亡抑制基因c-IAP1、Bcl-x1在宮頸癌中表達(dá)上調(diào),Bcl2下調(diào)。(2)相對于宮頸非病變組織,宮頸癌組織在RNA水平上高表達(dá)抗凋亡分子c-IAP1、 Bcl-x1,低表達(dá)Bcl2；蛋白水平上高表達(dá)抗凋亡分子c-IAP1, Bcl-x1,低表達(dá)Bcl2。這些基因在宮頸癌與宮頸非病變組織間的基因表達(dá)水平均存在顯著性差異,驗(yàn)證了基因芯片檢測的結(jié)果。結(jié)論：(1)獲得的宮頸癌癌變的生物分子標(biāo)志譜及篩選出的腫瘤標(biāo)志基因,對于研究新疆宮頸癌發(fā)生的分子機(jī)制及宮頸癌的臨床早期診療具有重要意義,差異表達(dá)基因的研究有助于我們對宮頸癌的發(fā)生發(fā)展的分子機(jī)制、信號傳導(dǎo)通路進(jìn)行進(jìn)一步的認(rèn)識。(2)宮頸癌的發(fā)生與凋亡調(diào)控失衡有密切關(guān)系,宮頸癌組織中IAP家族和Bcl2家族抗凋亡蛋白高表達(dá)可能在宮頸癌抗凋亡機(jī)制中起著重要作用,這些基因不僅可以用于宮頸癌的易感性預(yù)測、早期診斷及疾病監(jiān)測,對于其分子靶向治療的開展也具有重要的指導(dǎo)意義。
[Abstract]:Objective: to identify the differentially expressed genes in Uygur cervical cancer and non-pathological tissues of cervix uteri by using gene chip technology from the perspective of gene expression profile difference, and to verify the apoptosis-related genes. To explore the pathogenesis of cervical cancer in Uygur nationality and its relationship with clinicopathological indexes. Methods:. In order to screen differentially expressed genes in Xinjiang Uygur uterine leiomyoma, 5 cases of non-pathological cervix tissues and 5 cases of cervical cancer tissues were collected for gene chip screening of genome-wide expression profile. Real-time fluorescent quantitative PCR and immunohistochemistry were used to detect Bcl2P Bcl-x1 c-IAP1 in 21 non-pathological tissues of cervical carcinoma. The relationship between the expression level of each molecule and the corresponding clinicopathological indexes was analyzed. Results the whole genome oligonucleotide gene chip of Affymetrix was used. The differences of 5 pairs of invasive cervical cancer specimens and cervical non-pathological tissues of 18947 gene expression profiles were studied at the same time. The results showed that: compared with cervical non-pathological tissues. A total of 2758 differentially expressed genes were screened, among which 1326 genes were up-regulated and 1432 genes were down-regulated. These genes belong to different pathways, and 10 genes are known to be related to tumor apoptosis. Seven of the up-regulated genes belong to apoptosis-related pathway genes, and the apoptosis suppressor gene c-IAP1Bcl-x1 is up-regulated in cervical cancer. Compared with non-pathological tissues of cervix cervix, Bcl2 down-regulated c-IAP1, Bcl-x1 and Bcl-x1 at RNA level. High expression of anti-apoptotic molecules c-IAP1, Bcl-x1, and low expression of Bcl2.There was significant difference in the expression of these genes between cervical cancer and non-pathological tissues of cervix. Conclusion the biomolecular marker spectrum of cervical cancer carcinogenesis and the tumor marker gene were obtained. It is of great significance to study the molecular mechanism of cervical cancer in Xinjiang and the early clinical diagnosis and treatment of cervical cancer. The study of differentially expressed genes is helpful to the molecular mechanism of the occurrence and development of cervical cancer. Signal transduction pathway for further understanding. 2) the occurrence of cervical cancer is closely related to the imbalance of apoptosis regulation. The overexpression of anti-apoptotic proteins of IAP family and Bcl2 family may play an important role in the anti-apoptosis mechanism of cervical cancer. These genes can not only be used to predict the susceptibility of cervical cancer. Early diagnosis and disease surveillance are also of great significance for the development of molecular targeted therapy.
【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R737.33

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