From cirrhosis to hepatocellular carcinoma: An investigation into hepatitis C viral oncogenesis

Jihad Aljabban; Nilay Danis; Merve Gurakar; Kamal Khorfan; Nabeal Aljabban; Cem Simsek; Hussam Salhi; Maryam Panahiazar; Dexter Hadley; Ahmet Gurakar; Behnam Saberi

doi:10.14744/hf.2019.0002

From cirrhosis to hepatocellular carcinoma: An investigation into hepatitis C viral oncogenesis

Hepatol Forum. 2020 Jan 17;1(1):1-7. doi: 10.14744/hf.2019.0002. eCollection 2020 Jan.

Authors

Affiliations

¹ Ohio State University College of Medicine, Columbus, Ohio, USA.
² Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
³ Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁴ Henry Ford Health Systems, Detroit, Michigan, USA.
⁵ Penn State College of Medicine, Hershey, Pennsylvania 17033.
⁶ Institute for Computational Health Sciences, University of California, San Francisco, California 94158.
⁷ Icahn School of Medicine at Mount Sinai Division of Liver Diseases, New York, New York, USA.

Abstract

Background and aim: Hepatitis C is a leading cause of chronic liver disease and hepatocellular carcinoma (HCC). Understanding the evolution and biology of HCC among HCV patients may lead to novel therapeutic avenues and risk stratification.

Material and methods: Using meta-analysis platform STARGEO, we performed two separate meta-analyses as follows: 357 HCV-related HCC tumor samples with 220 adjacent non-tumor samples and 92 HCV-related cirrhotic liver samples with 53 healthy liver samples as a control. Then, we analyzed the signature in Ingenuity Pathway Analysis.

Results: HCV cirrhosis analysis demonstrated LPS/IL-1 mediated inhibition of RXR function, LXR/RXR activation, sirtuin signaling, IL-10 signaling and hepatic fibrosis/stellate cell activation as top canonical pathways. IL1β, TNF, and TGF-β1 were top upstream regulators. Cellular morphologic and signaling changes were noted through the up-regulation of RGS1/2, WNT receptor FZD7, the TGF-β1-induced gap junction gene GJA1, and the zinc finger transcription factor repressor SNAI2. Apoptosis was inhibited through the down-regulation of OMA1. Metabolic dysfunction was noted through the down-regulation of SCLY and CBS. HCV-related HCC analysis showed FXR/RXR and LXR/RXR signaling, LPS/IL1-mediated inhibition of RXR activation, and melatonin degradation as top canonical pathways.

Conclusion: Our results suggest that the genetic changes in the setting of chronic HCV infection predispose patients to developing HCC.

Keywords: HCC; HCV; STARGEO.

Abstract

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