基于生物信息学分析的人恶性肿瘤中非编码RNA基因的功能探索

发布时间：2018-07-04 07:40

本文选题：基于 + 生物　；参考：《北京协和医学院》2017年硕士论文

【摘要】：研究背景:雌激素受体信号调控着乳腺的众多生理过程,该信号通路的功能异常与乳腺癌的发生、演进、转归、内分泌治疗耐药等方面密切相关。非编码RNA是能够通过各个层面调控基因表达,然而已经被发现和研究的雌激素受体调控的长链非编码RNA很少。研究方法:我们从GEO数据库中下载Affymatrix Hgu133 Plus 2表达谱基因芯片数据,并使用ncFANs提供的芯片注释文件对芯片的探针进行注释。通过使用Limma包提供的差异表达算法鉴定雌激素受体α激动相关的长链非编码RNA。同时使用ncFNAs构建出蛋白质编码基因--长链非编码基因共表达网络预测雌激素受体α激动相关的长链非编码RNA的功能。进一步在雌激素受体阳性的乳腺癌患者队列中验证了雌激素受体α激动相关的长链非编码RNA的临床预后意义。研究结果:在这个研究中,我们使用表达谱基因芯片鉴定出33条与雌激素受体α激动相关的长链非编码RNA,蛋白质编码基因--长链非编码基因共表达网络分析结果表明15条雌激素受体α激动相关的长链非编码RNA的功能与细胞有丝分裂、DNA损伤修复等过程相关。Kaplan-Meier分析发现使用基于随机森林的递归特征选择算法选取的5条雌激素受体α激动相关的长链非编码RNA与雌激素受体阳性的乳腺癌患者的内分泌治疗耐药生存和远处转移显著相关。研究结论:我们的研究结果表明,雌激素受体α激动相关的长链非编码RNA可能作为指导雌激素受体阳性的乳腺癌患者内分泌治疗的生物标记物,并且可以为深入探索研究雌激素受体信号通路的功能提供新的视角。研究背景我国肝细胞肝癌(Hepatocellular Carcinoma,HCC)发病率和死亡率在过去的10到20年间在众肿瘤中稳居前三,85%的HCC与HBV慢性感染相关。在HBV感染的过程中,HBVDNA会整合到人类的基因组中促进HCC的发生。研究方法:在这个研究中,我们从Dr.VIS V2.0数据库中下载了2199个HBV病毒整合位点,并将整合位点回帖到第19版人类参考基因组上,将整合位点上下游1MB范围内的基因注释为整合位点先关的基因。然后我们对HBV病毒整合位点在癌和癌旁组织中的每一条染色体上的分布情况进行详细统计和可视化。研究结果:通过将整合位点回帖到第19版人类参考基因组上,我们获得1377个整合位点相关的蛋白质编码基因和767整合位点相关的长链非编码RNA基因。23.1%的整合位点相关的蛋白质编码基因被整合多于2次,24.7%整合位点相关的长链非编码RNA基因被整合大于2次,仅有4.8%的病毒整合位点相关的基因同时在癌和癌旁组织中同时出现。在癌组织中HBV病毒整合更倾向于分布在第5、8、10和19号染色体上,而在癌旁组织中,HBV病毒整合更倾向于分布在第1和2号染色体上。在癌组织中,每条染色体上的脆性位点数量与病毒整合位点的数量相关性低于癌旁组织。功能富集分析发现,在癌组织中的整合位点相关的蛋白质编码基因与肿瘤的发生相关。此外,根据NONCODEV4数据库注释结果,肿瘤组织中高频整合的IncRNA与端粒活性的保持,蛋白质修饰过程和染色体定位等功能相关。我们的数据表明病毒整合的分布可能存在一定的偏好性并非完全随机分布。癌和癌旁组织中的整合位点分布截然不同,部分病毒整合位点可能促进肿瘤的发生。
[Abstract]:Background: estrogen receptor signaling regulates many physiological processes in the breast. The dysfunction of the signal pathway is closely related to the occurrence, evolution, transformation, and drug resistance of the breast cancer. The non coded RNA is the length of the estrogen receptor that can regulate the expression of the gene through various levels, but the regulation of estrogen receptor has been discovered and studied. Chain non coding RNA is rare. Research methods: we downloaded the Affymatrix Hgu133 Plus 2 expression gene chip data from the GEO database and annotated the microchip probes using the chip annotation files provided by ncFANs. By using the differential expression algorithm provided by the Limma packet, we identify the long chain non coded RNA. identical with the estrin receptor alpha activation. NcFNAs was used to construct a protein coding gene, a long chain noncoding gene co expression network, to predict the function of the long chain noncoding RNA associated with estrogen receptor alpha excitation. The clinical prognostic significance of the estrogen receptor alpha induced long chain noncoding RNA was further verified in the cohort of estrogen receptor positive breast cancer patients. Fruit: in this study, we used expression gene chip to identify 33 long chain non coded RNA associated with estrogen receptor alpha activation. The protein encoding gene, a long chain non coding gene co expression network analysis results showed that 15 estrogen receptor alpha induced long chain noncoding RNA functions and cell mitosis, DNA damage repair. Complex process related.Kaplan-Meier analysis found that 5 estrogen receptor alpha agonist long chain non coded RNA and estrogen receptor positive breast cancer patients were significantly associated with endocrine therapy resistant survival and distant metastasis using a recursive feature selection algorithm based on random forest. The long chain non coding RNA associated with estrogen receptor alpha activation may serve as a biomarker for endocrine therapy for estrogen receptor positive breast cancer patients, and can provide a new perspective for exploring the function of the estrogen receptor signaling pathway. Background the pathogenesis of hepatocellular carcinoma (Hepatocellular Carcinoma, HCC) in China Rate and mortality rate in the past 10 to 20 years in the first three, 85% of the HCC and HBV chronic infection. In the process of HBV infection, HBVDNA will be integrated into the human genome to promote the occurrence of HCC. In this study, we downloaded 2199 HBV virus integration sites from the Dr.VIS V2.0 database and will integrate them. The site replies to the nineteenth version of the human reference genome and annotate the gene in the 1MB range of the upper and lower reaches of the integrated site as a gene for the integration site. Then we make a detailed statistics and visualization of the distribution of HBV virus integration sites on each chromosome in cancer and para cancerous tissues. On the nineteenth version of the human reference genome, we obtained 1377 integration locus related protein coding genes and 767 integrat related long chain non coding RNA gene.23.1% integration sites associated protein coding genes more than 2 times, 24.7% integrated loci related long chain non coded RNA genes were integrated more than 2 times, only 4. The gene associated with the viral integration site of.8% occurs simultaneously in cancer and para cancerous tissues. The integration of HBV virus is more likely to be distributed on chromosomes 5,8,10 and 19 in the cancer tissues, and the integration of HBV virus is more likely to be distributed on chromosome first and second in the para cancerous tissues. The quantitative correlation between the quantity and the integration site of the virus is lower than that of the paracancerous tissue. Functional enrichment analysis shows that the protein encoding genes associated with the integration site in the cancer tissues are related to the occurrence of tumor. In addition, the high frequency integrated IncRNA and telomere activity in the tumor tissue, the protein modification process in the tumor tissue, are related to the NONCODEV4 database. Our data show that the distribution of virus integration may not be completely random distribution. The distribution of integration sites in cancer and para cancerous tissues is completely different, and some viral integration sites may promote the occurrence of tumor.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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