發(fā)布時間：2018-07-04 07:40

  本文選題：基于 + 生物��； 參考：《北京協(xié)和醫(yī)學(xué)院》2017年碩士論文

【摘要】：研究背景:雌激素受體信號調(diào)控著乳腺的眾多生理過程,該信號通路的功能異常與乳腺癌的發(fā)生、演進、轉(zhuǎn)歸、內(nèi)分泌治療耐藥等方面密切相關(guān)。非編碼RNA是能夠通過各個層面調(diào)控基因表達,然而已經(jīng)被發(fā)現(xiàn)和研究的雌激素受體調(diào)控的長鏈非編碼RNA很少。研究方法:我們從GEO數(shù)據(jù)庫中下載Affymatrix Hgu133 Plus 2表達譜基因芯片數(shù)據(jù),并使用ncFANs提供的芯片注釋文件對芯片的探針進行注釋。通過使用Limma包提供的差異表達算法鑒定雌激素受體α激動相關(guān)的長鏈非編碼RNA。同時使用ncFNAs構(gòu)建出蛋白質(zhì)編碼基因--長鏈非編碼基因共表達網(wǎng)絡(luò)預(yù)測雌激素受體α激動相關(guān)的長鏈非編碼RNA的功能。進一步在雌激素受體陽性的乳腺癌患者隊列中驗證了雌激素受體α激動相關(guān)的長鏈非編碼RNA的臨床預(yù)后意義。研究結(jié)果:在這個研究中,我們使用表達譜基因芯片鑒定出33條與雌激素受體α激動相關(guān)的長鏈非編碼RNA,蛋白質(zhì)編碼基因--長鏈非編碼基因共表達網(wǎng)絡(luò)分析結(jié)果表明15條雌激素受體α激動相關(guān)的長鏈非編碼RNA的功能與細胞有絲分裂、DNA損傷修復(fù)等過程相關(guān)。Kaplan-Meier分析發(fā)現(xiàn)使用基于隨機森林的遞歸特征選擇算法選取的5條雌激素受體α激動相關(guān)的長鏈非編碼RNA與雌激素受體陽性的乳腺癌患者的內(nèi)分泌治療耐藥生存和遠處轉(zhuǎn)移顯著相關(guān)。研究結(jié)論:我們的研究結(jié)果表明,雌激素受體α激動相關(guān)的長鏈非編碼RNA可能作為指導(dǎo)雌激素受體陽性的乳腺癌患者內(nèi)分泌治療的生物標記物,并且可以為深入探索研究雌激素受體信號通路的功能提供新的視角。研究背景我國肝細胞肝癌(Hepatocellular Carcinoma,HCC)發(fā)病率和死亡率在過去的10到20年間在眾腫瘤中穩(wěn)居前三,85%的HCC與HBV慢性感染相關(guān)。在HBV感染的過程中,HBVDNA會整合到人類的基因組中促進HCC的發(fā)生。研究方法:在這個研究中,我們從Dr.VIS V2.0數(shù)據(jù)庫中下載了2199個HBV病毒整合位點,并將整合位點回帖到第19版人類參考基因組上,將整合位點上下游1MB范圍內(nèi)的基因注釋為整合位點先關(guān)的基因。然后我們對HBV病毒整合位點在癌和癌旁組織中的每一條染色體上的分布情況進行詳細統(tǒng)計和可視化。研究結(jié)果:通過將整合位點回帖到第19版人類參考基因組上,我們獲得1377個整合位點相關(guān)的蛋白質(zhì)編碼基因和767整合位點相關(guān)的長鏈非編碼RNA基因。23.1%的整合位點相關(guān)的蛋白質(zhì)編碼基因被整合多于2次,24.7%整合位點相關(guān)的長鏈非編碼RNA基因被整合大于2次,僅有4.8%的病毒整合位點相關(guān)的基因同時在癌和癌旁組織中同時出現(xiàn)。在癌組織中HBV病毒整合更傾向于分布在第5、8、10和19號染色體上,而在癌旁組織中,HBV病毒整合更傾向于分布在第1和2號染色體上。在癌組織中,每條染色體上的脆性位點數(shù)量與病毒整合位點的數(shù)量相關(guān)性低于癌旁組織。功能富集分析發(fā)現(xiàn),在癌組織中的整合位點相關(guān)的蛋白質(zhì)編碼基因與腫瘤的發(fā)生相關(guān)。此外,根據(jù)NONCODEV4數(shù)據(jù)庫注釋結(jié)果,腫瘤組織中高頻整合的IncRNA與端�；钚缘谋３�,蛋白質(zhì)修飾過程和染色體定位等功能相關(guān)。我們的數(shù)據(jù)表明病毒整合的分布可能存在一定的偏好性并非完全隨機分布。癌和癌旁組織中的整合位點分布截然不同,部分病毒整合位點可能促進腫瘤的發(fā)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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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