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Identification of key regulatory pathways and regulators in the pathogenesis of hepatitis C virus-induced hepatocellular carcinoma
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  • Guolin Chen,
  • Yongguo Li,
  • Yingjie Ma,
  • Xue Tan
Guolin Chen
First Affiliated Hospital of Harbin Medical University
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Yongguo Li
First Affiliated Hospital of Harbin Medical University
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Yingjie Ma
First Affiliated Hospital of Harbin Medical University
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Xue Tan
First Affiliated Hospital of Harbin Medical University
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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.