a comprehensive analysis of the dynamic biological networks in hcv induced hepatocarcinogenesis综合分析的动态在丙肝病毒诱导hepatocarcinogenesis生物网络.pdfVIP

A Comprehensive Analysis of the Dynamic Biological Networks in HCV Induced Hepatocarcinogenesis 1 2 1,3 Bing He , Hao Zhang , Tieliu Shi * 1 Center for Bioinformatics and Computational Biology, The Institute of Biomedical Sciences, School of Life Science, East China Normal University, Shanghai, China, 2 Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China, 3 Shanghai Information Center for Life Sciences, Chinese Academy of Science, Shanghai, China Abstract Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, which is closely related to hepatitis C and cirrhosis. The molecular mechanisms underlying the hepatocarcinogenesis induced by HCV infection remain clarified from a standpoint of systems biology. By integrating data from protein-protein interactions, transcriptional regulation, and disease related microarray analysis, we carried out a dynamic biological network analysis on the progression of HCV induced hepatocarcinogenesis, and systematically explored the potentially disease-related mechanisms through a network view. The dysfunctional interactions among proteins and deregulatory relationships between transcription factors and their target genes could be causes for the occurrence and progression of this disease. The six pathologically defined disease stages in the development and progression of HCC after HCV infection were included in this study. We constructed disease-related biological networks for each disease stage, and identified progression-related sub-networks that potentially play roles in the developmental stage of the corresponding disease and participate in the later stage of cancer progression. In addition, we identified novel risk factors related to