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

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

【摘要】：目的：從基因表達譜差異的角度,利用基因芯片技術尋找維吾爾族宮頸癌與宮頸非病變組織不同的相關基因差異表達情況,并對凋亡相關基因驗證,探討維吾爾族宮頸癌的發(fā)病機制及與臨床病理指標的關系。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譜基因芯片篩選差異表達基因,采用實時熒光定量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進行檢測,并分析各分子表達水平與相應臨床病理指標的關系。結(jié)果：(1)采用Affymetrix的全基因組寡核苷酸基因芯片,對5對浸潤性宮頸癌標本及宮頸非病變組織的18947個基因的表達譜差異同時進行了研究,結(jié)果顯示：與宮頸非病變組織相比,共篩選到差異表達基因2758個其中上調(diào)基因1326個,下調(diào)基因1432個,分屬不同的通路,已知與腫瘤凋亡發(fā)生相關的基因10個,表達上調(diào)的的基因中7個屬于凋亡相關通路基因。凋亡抑制基因c-IAP1、Bcl-x1在宮頸癌中表達上調(diào),Bcl2下調(diào)。(2)相對于宮頸非病變組織,宮頸癌組織在RNA水平上高表達抗凋亡分子c-IAP1、 Bcl-x1,低表達Bcl2；蛋白水平上高表達抗凋亡分子c-IAP1, Bcl-x1,低表達Bcl2。這些基因在宮頸癌與宮頸非病變組織間的基因表達水平均存在顯著性差異,驗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志譜及篩選出的腫瘤標志基因,對于研究新疆宮頸癌發(fā)生的分子機制及宮頸癌的臨床早期診療具有重要意義,差異表達基因的研究有助于我們對宮頸癌的發(fā)生發(fā)展的分子機制、信號傳導通路進行進一步的認識。(2)宮頸癌的發(fā)生與凋亡調(diào)控失衡有密切關系,宮頸癌組織中IAP家族和Bcl2家族抗凋亡蛋白高表達可能在宮頸癌抗凋亡機制中起著重要作用,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.
【學位授予單位】：新疆醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R737.33

【參考文獻】

相關期刊論文 前10條

1 謝東華,唐孝達,夏術階,譚建明,王祥慧,蔡勇;核轉(zhuǎn)錄因子κB在膀胱癌中的表達及臨床意義[J];癌癥;2002年06期

2 胡靜姿;劉惠敏;李玉莉;何金;朱維建;;Bcl-2、Bcl-x_L和Bax在結(jié)直腸癌中的表達[J];第二軍醫(yī)大學學報;2006年03期

3 王峰;王留興;何偉;朱利楠;趙培榮;樊青霞;;Stathmin基因在食管鱗癌中的表達及生物學意義[J];南方醫(yī)科大學學報;2010年07期

4 李昕,李建民,楊志平,許復郁;Bcl-x_L及DNA-PKcs在ⅡB期骨肉瘤中的表達及臨床意義[J];中國骨腫瘤骨病;2005年01期

5 李顯文,楊羅艷,王紅珊;膀胱癌腫瘤組織中bcl-x基因mRNA的表達及其臨床意義[J];醫(yī)學臨床研究;2004年03期

6 趙玲;國內(nèi)外宮頸癌的發(fā)病狀況及趨勢[J];中國計劃生育學雜志;2003年08期

7 李輝,王繼群,曾子華,付向軍,張偉軍;凋亡相關基因c-IAP2和caspase-4在頭頸部低分化鱗狀細胞癌中的表達及意義[J];臨床耳鼻咽喉科雜志;2003年12期

8 王艷;任金海;林鳳茹;陳靜;杜行嚴;;c-IAP1與bcl-2基因在急性白血病中的表達及臨床意義[J];臨床薈萃;2005年23期

9 瑪依努爾·尼牙孜;李麗;陳鳳;章文華;朱開春;劉新偉;熱孜亞·買買提孜;孫振柱;趙麗霞;張詢;潘秦鏡;劉新伏;武艷萍;喬友林;;新疆維吾爾族女性人乳頭瘤病毒感染與宮頸癌相關性的流行病學調(diào)查[J];臨床腫瘤學雜志;2011年04期

10 史朝暉,姜希宏,劉建民;核因子-κBp65及bcl-x_L基因在胰腺癌組織中表達及意義[J];中國現(xiàn)代普通外科進展;2004年03期

，

本文編號：1425315