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BioMed Research International
Volume 2015, Article ID 391475, 27 pages
Research Article

Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

1Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hisnchu 30013, Taiwan
2Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan
3Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan

Received 27 February 2015; Revised 23 April 2015; Accepted 23 April 2015

Academic Editor: Zheng Li

Copyright © 2015 Yung-Hao Wong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.