title: Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages.
authors.affiliation: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hisnchu 30013, Taiwan.
authors.forename: Yung-Hao
authors.initials: YH
authors.lastname: Wong
authors.affiliation: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hisnchu 30013, Taiwan.
authors.forename: Chia-Chou
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
authors.forename: Ting-Shou
authors.initials: TS
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Chang
authors.affiliation: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hisnchu 30013, Taiwan.
authors.forename: Bor-Sen
authors.initials: BS
authors.lastname: Chen
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D060066:Protein Interaction Maps / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D049490:Systems Biology / Q000379:methods
chemical_list: D015415:Biomarkers; D011506:Proteins