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Study On The Differential Gene Exppression Profiles Of Liver Cirrhosis On Hepatocellular Carcinoma Based On Bioinformatics

Posted on:2014-11-01Degree:MasterType:Thesis
Country:ChinaCandidate:J ChenFull Text:PDF
GTID:2254330425950225Subject:Biochemistry and Molecular Biology
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Hepatocellular carcinoma(HCC) is a malignant tumor of liver system, which has the relation with the race and local environment. There are over667,000people were diagnosed with liver cancer on a global scale, and60,000died of liver tumor.55%of new HCC cases were come from China. The incidence rate of HCC ranks the fifth among all tumors in the world, and the mortality ranks the third. At present, a liver cancer5year survival rate was still less than10%, which is only inferior to the pancreas cancer (4.4%) in the malignant tumor disease.HCC is a malignant tumor occurred in liver lobe. But the pathogenesis of HCC has not yet been fully determined. Recent studies show that hepatitis virus infection, aflatoxin toxins and other chemical carcinogens induced intake are risk factors for liver cancer. Recent studies show HCC carcinogenesis is a multi-gene and multi-step complicated process. The mechanism of molecular regulation is obscure. Lots of the patients of HCC in China have hepatitis B history, however, the incidence rate of HCC in patients of hepatitis B without cirrhosis is far lower than that with cirrhosis. Almost84.6%of HCC come with cirrhosis, whereas49.9%of cirrhosis will develop into HCC, which indicates HBV、cirrhosis、HCC is a three-step process. Thus, to found the expression of oncogene and suppressor gene in cirrhotic liver is not only important to find the gene changes in HCC early stage but also essential to have an overview of the carcinogenesis of HCC.As a high-throughput and integrating new technology, Gene chip can monitor a large number of mRNA transcriptions. Gene chip technological is one of the most important methods in gene function study, which has been widely used in gene expression, disease diagnosis, drug screening and other fields. With the development of high-throughput microarray technology and DNA sequencing, enormous data has been generated. Therefore, a new method should be developed. Bioinformatics is an interdisciplinary, including modern biology, medical science, informatics, computer science, biostatistics and mathematics, which plays a key role in design of drugs, analyses of gene polymorphism, control of gene expression, identifies of related gene in diseases, predictions of the structure and function of gene production, etc.The results came from BRB Array Tools tools tools analyzing the data of Agilent human genome4×44K microarrays assay showed that there were1865features were differentially expressed in the liver cirrhosis on the basis of p<0.01,392of them up-regulated,1473of them down-regulated. When adjusted p value to <0.001, there were only680features were differentially expressed in the liver cirrhosis,147of them up-regulated,533of them down-regulated.Pathway analysis and functional annotation of these differentially expressed genes by the GATHER, PANTHER, DAVID bioinformatics tools and GSEA methods showed that these genes associated with the following biological process: sensory perception of smell, G-protein coupled receptor protein signaling pathway, keratinization, cell surface receptor linked signal transduction and keratinocyte differentiation; the cellular component:intermediate filament, cytoskeletal part, keratin filament, plasma membrane and dynein complex; the following molecular function:olfactory receptor activity, interferon-alpha/beta receptor binding, extracellular matrix structural constituent, cytokine activity, glucuronosyltransferase activity and receptor regulator activity; and the following biological pathways: Insulin signaling pathway, Cytokine-cytokine receptor interaction, Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway, Wnt signaling pathway, Huntington disease, Nicotine degradation, Cadherin signaling pathway and Olfactory transduction and Regulation of autophagy, and two of the former are the most significant.To further understand the interaction networks among these differentially expressed genes, proteins interactions searched from HPRD database based on these differentially expressed proteins of were analyzed by Cytoscape. Using Cytoscape program, the hub proteins of protein-protein interaction (PPI) network were obtained, including5over-expressed proteins(DCTN1、 ING1、LRP1、PDLIM7and VHL) and5over-expressed proteins(ATM、ITGB4、KRT18、MDFI and CSF2RB).
Keywords/Search Tags:Liver cirrhosis, Gene chip, Bioinformatics, Differential genes, protein-protein interaction
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