本文選題：宮頸癌　切入點(diǎn)：缺氧　出處：《廣西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：第一部分基于高通量數(shù)據(jù)對(duì)宮頸癌缺氧生物標(biāo)志物的分析目的:在 GEO (gene expression omnibus)和 TCGA (the cancer genome atlas)數(shù)據(jù)庫中挖掘?qū)m頸癌缺氧標(biāo)志物并對(duì)其預(yù)后進(jìn)行生存分析。方法:利用GEO數(shù)據(jù)庫中宮頸癌表達(dá)譜(GSE75034)缺氧組織和非缺氧組織中的數(shù)據(jù)進(jìn)行差異性分析,再運(yùn)用基因功能分析(gene ontology, GO)與通路富集分析(kyoto encyclopedia of genes and genomes,KEGG)篩選出相關(guān)的通路和相關(guān)功能的基因,結(jié)合TCGA數(shù)據(jù)庫中宮頸癌的數(shù)據(jù)對(duì)其預(yù)后運(yùn)用Kaplan- Meier與log- rank檢驗(yàn)方法進(jìn)行生存分析。結(jié)果:顯示有337個(gè)基因表達(dá)存在明顯差異,缺氧組織中上調(diào)的基因有184個(gè),下調(diào)的有153個(gè)。GO分析顯示這些基因與免疫反應(yīng),炎癥反應(yīng),細(xì)胞增殖,血管形成等有關(guān);KEGG分析顯示主要富集在TNF信號(hào)通路,PI3K-Akt信號(hào)通路,HIF-1信號(hào)通路等。生存分析顯示富集在HIF-1通路上的PA][-1、BCL-2、HK-2與宮頸癌病人預(yù)后相關(guān),其中PAI-1、HK-2是預(yù)后的危險(xiǎn)因素,高表達(dá)組與患者生存期縮短相關(guān),BCL-2是保護(hù)因素,高表達(dá)組與患者生存期延長相關(guān)。結(jié)論:PAI-1、BCL-2、HK-2可以作為宮頸癌缺氧生物標(biāo)志物,與宮頸癌病人的預(yù)后相關(guān),為后續(xù)的研究提供新思路。第二部分基于高通量數(shù)據(jù)對(duì)肝癌血管侵襲標(biāo)志物的分析目的:通過對(duì) GEO(Gene Expression Omnibus)與 TCGA(The Cancer Genome Atlas)數(shù)據(jù)庫分析,挖掘肝癌血管侵襲相關(guān)的microRNA,并對(duì)其預(yù)后和可能機(jī)制進(jìn)行分析。方法:利用GEO數(shù)據(jù)庫獲得肝癌血管侵襲microRNA與基因數(shù)據(jù)(GSE67140, GSE20238)進(jìn)行聯(lián)合分析,對(duì)5種侵襲能力不同的細(xì)胞系(SNU423、SNU449、HepG2、Hep3B、SNU398)表達(dá)譜進(jìn)行差異分析,并在81例血管侵襲陽性組織樣本與91例血管侵襲陰性組織樣本中驗(yàn)證差異分析結(jié)果。結(jié)合TCGA數(shù)據(jù)庫中362例肝癌病人的數(shù)據(jù)對(duì)其預(yù)后進(jìn)行分析,并對(duì)microRNA所調(diào)控的基因進(jìn)行GO與KEGG分析,結(jié)合基因表達(dá)譜數(shù)據(jù)構(gòu)建基因調(diào)控網(wǎng)絡(luò)。結(jié)果:hsa-mir-l180、hsa-mir-149、hsa-mir-744、hsa-mir-940 在侵襲能力強(qiáng)的肝癌細(xì)胞和有血管侵襲的肝癌組織中表達(dá)上調(diào)(logFC1,P0.05)。生存分析顯示 hsa-mir-1180(H= 1.623, 95%CI= 1.114-2.365;P=0.012),hsa-mir-149 (HR = 2.4, 95% CI= 1.639-3.514; P 0.001) , hsa-mir-744 (HR=1.679, 95%CI= 1.161-2.427;P = 0.006) , hsa-mir-940 (HR = 1.704, 95%CI= 1.188-2.443;P = 0.004)是肝癌病人預(yù)后獨(dú)立危險(xiǎn)因素,高表達(dá)與患者生存期縮短顯著相關(guān)(P 0.05)。GO與KEGG分析其機(jī)制可能與免疫反應(yīng),細(xì)胞粘附,緊密連接等信號(hào)通路有關(guān),基因調(diào)控網(wǎng)絡(luò)分析顯示CYP8B1,TAT,SLC10A1等基因可能在肝癌血管侵襲中發(fā)揮重要作用。結(jié)論:本研究通過對(duì)TCGA與GEO數(shù)據(jù)庫的挖掘,初步發(fā)現(xiàn)hsa-mir-1180、hsa-miR-149、hsa-mir-744、hsa-mir-940對(duì)肝癌的預(yù)后有影響,可以作為肝癌預(yù)后的生物標(biāo)志物進(jìn)一步研究。
[Abstract]:Part one: analysis of hypoxia biomarkers in cervical cancer based on high-throughput data objective: to explore the anoxic biomarkers of cervical cancer in GEO gene expression omnibusand TCGA the cancer genome atlas database and to analyze the prognosis of hypoxia biomarkers of cervical cancer. Methods:. The difference was analyzed between anoxic tissue and non-anoxic tissue by using the expression profile of cervical cancer (GSE75034) in GEO database. Gene functional analysis (GOA) and pathway enrichment analysis (KEGG) were used to screen the genes related to the pathway and related functions. Combined with the data of cervical cancer in TCGA database, Kaplan-#en1# and log-#en2# test were used to analyze the prognosis of cervical cancer. Results: there were significant differences in the expression of 337 genes, and 184 genes were up-regulated in hypoxic tissues. There are 153 down-regulated. Go analysis shows that these genes are associated with immune response, inflammatory response, cell proliferation, Angiogenesis and KEGG analysis showed that the TNF signaling pathway was mainly concentrated in the PI3K-Akt signaling pathway and HIF-1 signaling pathway. Survival analysis showed that PA enriched in the HIF-1 pathway [-1 BCL-2HK-2] was associated with the prognosis of patients with cervical cancer, and PAI-1HK-2 was a prognostic risk factor. BCL-2 was a protective factor in high expression group and prolonged survival time in high expression group. Conclusion the high expression group can be used as a biomarker of cervical cancer anoxia and the prognosis of cervical cancer patients. Part 2: analysis of vascular invasion markers of hepatocellular carcinoma based on high-throughput data. Objective: to analyze the GEO(Gene Expression Omnibus and TCGA(The Cancer Genome Atlas database. The prognosis and possible mechanism of microRNAs were analyzed. Methods: GEO database was used to obtain microRNA and GSE67140, GSE20238). The expression profiles of SNU423 SNU449 (HepG2 Hep3BnU SNU398) in 5 cell lines with different invasion ability were analyzed. The results of differential analysis were verified in 81 cases of vascular invasion positive tissue samples and 91 cases of vascular invasion negative tissue samples. The prognosis was analyzed by combining the data of 362 cases of liver cancer patients in TCGA database. The genes regulated by microRNA were analyzed by go and KEGG. Results the expression of hsa-mir-l180 hsa-mir-149nhsa-mir-744hsa-mir-940 was upregulated in invasive hepatoma cells and vascularly invasive liver cancer tissues. Survival analysis showed that hsa-mir-1180 hsa-mir-1180 hsa-mir-149HR = 1.114-2.365hsa-mir-149HR = 2.44,95% CI = 1.639-3.514; P 0.001), hsa-mir-744, P0.012Hsa-mir-149 HR = 2.44,95% CI = 1.639-3.514; P 0.001), HSA-mir-1180H = 1.6233,95CI= 1.114-2.365Hsa-mir-149 HR = 2.44,95% CI = 1.639-3.514; P 0.001). HRN 1.679, 95 CI = 1.161-2.427g P = 0.006), hsa-mir-940 HR = 1.704, 95CI = 1.188-2.443 P = 0.004) are independent prognostic factors of HCC. The high expression of P 0.05).GO and KEGG may be related to the signal pathways such as immune response, cell adhesion, tight junction and so on. Gene regulation network analysis showed that CYP8B1TTATTATSLC10A1 might play an important role in the vascular invasion of HCC. Conclusion: hsa-mir-1180hsa-miR-149nhsa-mir-744hsa-mir-940 may play an important role in the prognosis of HCC. It can be used as a biomarker for prognosis of liver cancer.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.7;R737.33

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