Identifying the key genes and pathways in the progression of hepatitis C virus induced hepatocellular carcinoma using a systems biology approach
© Zheng and Zhao; licensee BioMed Central Ltd. 2011
Published: 5 August 2011
Incidence of hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) has been increasing in many developed countries including the United States and Europe during the recent years. Although many efforts have been made to understand the pathogenesis, the picture of its progression still remains elusive.
Materials and methods
We developed a systematic approach to identify deregulated biological networks in HCC by integrating gene expression profiles  with high-throughput protein-protein interaction data . Samples were grouped into five disease stages including normal, cirrhotic, dysplastic, early and advanced HCC. For each pair of consecutive stages, we compared gene expressions and then mapped these measures to the protein interaction network. Responsive subnetworks were then identified from these node weighted networks. The searching algorithm is adapted from a previous study , which expands the seed graphs under constrains of several parameters.
Overview of the responsive networks.
Dysplasia -early HCC
Early- advanced HCC
Our study uncovers a temporal spectrum of functional deregulation and prioritizes key genes and pathways in the progression of HCV induced HCC. Despite the confirmation of much knowledge in the pathogenesis of this disease, these findings also provide additional insights for further investigations.
We thank Drs. Scott Hiebert, William Tansey, Jingchun Sun and Peilin Jia and Mr. Jeffery Ewers for helpful discussions.
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