新疆维吾尔族宫颈癌组织中全基因组表达谱分析及与凋亡相关基因c-IAP1、Bcl-xl、Bcl2的检测

发布时间：2018-01-14 21:12

本文关键词：新疆维吾尔族宫颈癌组织中全基因组表达谱分析及与凋亡相关基因c-IAP1、Bcl-xl、Bcl2的检测　出处：《新疆医科大学》2014年博士论文　论文类型：学位论文

【摘要】：目的：从基因表达谱差异的角度,利用基因芯片技术寻找维吾尔族宫颈癌与宫颈非病变组织不同的相关基因差异表达情况,并对凋亡相关基因验证,探讨维吾尔族宫颈癌的发病机制及与临床病理指标的关系。方法：收集新疆维吾尔族子宫肌瘤的非病变宫颈组织及宫颈癌组织各5例用于全基因组表达谱基因芯片筛选差异表达基因,采用实时荧光定量PCR及免疫组化对45例宫颈癌,21例宫颈非病变组织中Bcl2、Bcl-x1、c-IAP1进行检测,并分析各分子表达水平与相应临床病理指标的关系。结果：(1)采用Affymetrix的全基因组寡核苷酸基因芯片,对5对浸润性宫颈癌标本及宫颈非病变组织的18947个基因的表达谱差异同时进行了研究,结果显示：与宫颈非病变组织相比,共筛选到差异表达基因2758个其中上调基因1326个,下调基因1432个,分属不同的通路,已知与肿瘤凋亡发生相关的基因10个,表达上调的的基因中7个属于凋亡相关通路基因。凋亡抑制基因c-IAP1、Bcl-x1在宫颈癌中表达上调,Bcl2下调。(2)相对于宫颈非病变组织,宫颈癌组织在RNA水平上高表达抗凋亡分子c-IAP1、 Bcl-x1,低表达Bcl2；蛋白水平上高表达抗凋亡分子c-IAP1, Bcl-x1,低表达Bcl2。这些基因在宫颈癌与宫颈非病变组织间的基因表达水平均存在显著性差异,验证了基因芯片检测的结果。结论：(1)获得的宫颈癌癌变的生物分子标志谱及筛选出的肿瘤标志基因,对于研究新疆宫颈癌发生的分子机制及宫颈癌的临床早期诊疗具有重要意义,差异表达基因的研究有助于我们对宫颈癌的发生发展的分子机制、信号传导通路进行进一步的认识。(2)宫颈癌的发生与凋亡调控失衡有密切关系,宫颈癌组织中IAP家族和Bcl2家族抗凋亡蛋白高表达可能在宫颈癌抗凋亡机制中起着重要作用,这些基因不仅可以用于宫颈癌的易感性预测、早期诊断及疾病监测,对于其分子靶向治疗的开展也具有重要的指导意义。
[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.
【学位授予单位】：新疆医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.33

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