基于高通量数据对宫颈癌和肝癌标志物的研究

发布时间：2018-03-26 22:29

本文选题：宫颈癌　切入点：缺氧　出处：《广西医科大学》2017年硕士论文

【摘要】：第一部分基于高通量数据对宫颈癌缺氧生物标志物的分析目的:在 GEO (gene expression omnibus)和 TCGA (the cancer genome atlas)数据库中挖掘宫颈癌缺氧标志物并对其预后进行生存分析。方法:利用GEO数据库中宫颈癌表达谱(GSE75034)缺氧组织和非缺氧组织中的数据进行差异性分析,再运用基因功能分析(gene ontology, GO)与通路富集分析(kyoto encyclopedia of genes and genomes,KEGG)筛选出相关的通路和相关功能的基因,结合TCGA数据库中宫颈癌的数据对其预后运用Kaplan- Meier与log- rank检验方法进行生存分析。结果:显示有337个基因表达存在明显差异,缺氧组织中上调的基因有184个,下调的有153个。GO分析显示这些基因与免疫反应,炎症反应,细胞增殖,血管形成等有关;KEGG分析显示主要富集在TNF信号通路,PI3K-Akt信号通路,HIF-1信号通路等。生存分析显示富集在HIF-1通路上的PA][-1、BCL-2、HK-2与宫颈癌病人预后相关,其中PAI-1、HK-2是预后的危险因素,高表达组与患者生存期缩短相关,BCL-2是保护因素,高表达组与患者生存期延长相关。结论:PAI-1、BCL-2、HK-2可以作为宫颈癌缺氧生物标志物,与宫颈癌病人的预后相关,为后续的研究提供新思路。第二部分基于高通量数据对肝癌血管侵袭标志物的分析目的:通过对 GEO(Gene Expression Omnibus)与 TCGA(The Cancer Genome Atlas)数据库分析,挖掘肝癌血管侵袭相关的microRNA,并对其预后和可能机制进行分析。方法:利用GEO数据库获得肝癌血管侵袭microRNA与基因数据(GSE67140, GSE20238)进行联合分析,对5种侵袭能力不同的细胞系(SNU423、SNU449、HepG2、Hep3B、SNU398)表达谱进行差异分析,并在81例血管侵袭阳性组织样本与91例血管侵袭阴性组织样本中验证差异分析结果。结合TCGA数据库中362例肝癌病人的数据对其预后进行分析,并对microRNA所调控的基因进行GO与KEGG分析,结合基因表达谱数据构建基因调控网络。结果:hsa-mir-l180、hsa-mir-149、hsa-mir-744、hsa-mir-940 在侵袭能力强的肝癌细胞和有血管侵袭的肝癌组织中表达上调(logFC1,P0.05)。生存分析显示 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)是肝癌病人预后独立危险因素,高表达与患者生存期缩短显著相关(P 0.05)。GO与KEGG分析其机制可能与免疫反应,细胞粘附,紧密连接等信号通路有关,基因调控网络分析显示CYP8B1,TAT,SLC10A1等基因可能在肝癌血管侵袭中发挥重要作用。结论:本研究通过对TCGA与GEO数据库的挖掘,初步发现hsa-mir-1180、hsa-miR-149、hsa-mir-744、hsa-mir-940对肝癌的预后有影响,可以作为肝癌预后的生物标志物进一步研究。
[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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.7;R737.33

【相似文献】