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Bioinformatics Analysis Of Hypoxic Markers In Cervical Cance And Vascular Invasion Markers In Hepatocellular Carcinoma Via High-throughput Data

Posted on:2018-03-26Degree:MasterType:Thesis
Country:ChinaCandidate:Q ChenFull Text:PDF
GTID:2334330518952821Subject:Epidemiology and Health Statistics
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Section 1 Bioinformatics analysis of hypoxic markers in cervical cancer via High-throughput dataPurpose: To investigate the hypoxic markers in cervical cancer and its prognostic value via GEO (gene expression omnibus) and TCGA (the cancer genome atlas) database.Methods: Methods: The datasets of cervical cancer were downloaded from GEO and TCGA database. Hypoxic markers in cervical cancer were explored via GSE75034 database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze gene functions. Kaplan- Meier and log- rank test were used to study the prognostic valuevia TCGA database.Results: 337 genes had different expression levels between hypoxic tissues and non-hypoxic tissues, of which 184 genes were upregulated and 153 genes were downregulated. GO analysis showed these genes were related to immune response, inflammation, cell proliferation, angiogenesis, etc. KEGG analysis showed that these genes were enriched in TNF signaling pathway, PI3K-Akt signaling pathway and HIF-1 signaling pathway. Moreover, TCGA data analysis showed PAI-1, BCL-2, HK-2 which enriched in HIF-1 signaling pathway were related to cervical cancer patient prognostic. High levels of PAI-1 and HK-2 expression were significantly correlated with shortened survival(P<0.05), which indicated a worse outcome, whereas high level of BCL-2 expression was significantly correlated with a prolonged survival (P<0.05),suggesting BCL-2 was a protective factor.Conclusions: Our results suggested that PAI-1, BCL-2 and HK-2 could be promising hypoxia biomarkers for the prognosis of cervical cancer.Section 2 Bioinformatics analysis of vascular invasion markers in hepatocellular carcinoma via High-throughput dataPurpose: To investigate the biomarkers in hepatocellular carcinoma (HCC) and their prognostic value via GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) database.Methods: The datasets of hepatocellular carcinoma were download from GEO(GSE67140 , GSE20238) and TCGA. We investigated the microRNA in SNU423, SNU449, HepG2, Hep3B, SNU398 cell lines which had low or high invasion capabilities. We verified them in 81 vascular invasion present hepatocellular carcinoma patients and 91 vascular invasion absent hepatocellular carcinoma patients. The prognostic value of these microRNAs were studied via TCGA database which obtained 362 hepatocellular carcinoma patients through Kaplan-Meier and Multivariate Cox proportional hazard analyses. The target genes were analyzed by GO and KEGG and construction of gene regulatory network in combination with gene expression profile data.Results: The expression of hsa-mir-1180, hsa-mir-149, hsa-mir-744 and hsa-mir-940 were both upregulated in high invasion capable cell lines(SNU423?SNU449) and vascular invasion present hepatocellular carcinoma patients (logFC > 1, P < 0.05). Survival analysis showed that hsa-mir-1180 (HR= 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) were independent risk factors for prognosis of patients with hepatocellular carcinoma(P < 0.05). The mechanism might be related to immune response, focal adhesion,adherens junction signaling pathways and so on, gene regulation network analysis showed that CYP8B1,TAT, SLC10A1 and other genes may play an important role in vascular invasion of hepatocellular carcinoma.Conclusion: With TCGA and GEO data mining, we found that hsa-mir-1180,hsa-miR-149, hsa-mir-744 and hsa-mir-940 are highly related to hepatocellular carcinoma prognosis, as further study biomarker related to prognosis of hepatocellular carcinoma.
Keywords/Search Tags:cervical cancer, hypoxic, High-throughput data, biomarker, hepatocellular carcinoma, vascular invasion, MicroRNA
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