Identification of key regulatory pathways and regulators in the
pathogenesis of hepatitis C virus-induced hepatocellular carcinoma
Abstract
Hepatitis virus infection is a leading cause of chronic liver diseases,
including cirrhosis and hepatocellular carcinoma (HCC). However, the
molecular mechanism by which hepatitis causes liver cancer remains
unclear. Additionally, new biomarkers for diagnosis, prognosis and
therapeutics are needed. Regulatory pathways play important roles in
many pathogenic processes, and identifying the pathways by which
hepatitis C virus (HCV) induces HCC may lead to better diagnosis and
treatment. We employed a systematic approach to identify important
regulatory pathways in this disease process, and found several important
regulators. First, three networks were constructed based on the gene
expression in patients with hepatitis alone, HCC alone, and hepatitis
with HCC. A priority algorithm was used to extract the regulatory
pathways from the networks, which were then scored based on the
disease-related genetic information to identify key pathways. After
integrating the regulatory pathways involved in the three networks, we
found key regulatory genes, including EZH2 and hsa-miR-155-5p. Based on
network analysis, it appeared that in HCC patients the abnormal
expression of genes and miRNAs were mostly caused by abnormal expression
of these key regulatory factors. This method may help researchers
discover the potential pathogenic factors of HCC and could also yield
new biomarkers for disease diagnosis.