The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression
Ciniso Sylvester Shabangu,
Phumelele Yvonne Siphepho,
Chia-Yang Li,
Wei-Chung Cheng,
Ming-Ying Lu,
Chung-Feng Huang,
Ming-Lun Yeh,
Chia-Yen Dai,
Jee-Fu Huang,
Wan-Long Chuang,
Zu-Yau Lin,
Ming-Lung Yu,
Shu-Chi Wang
Affiliations
Ciniso Sylvester Shabangu
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Phumelele Yvonne Siphepho
Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Chia-Yang Li
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Wei-Chung Cheng
Research Center for Cancer Biology, Graduate Institute of Biomedical Science, China Medical University, Taichung 406040, Taiwan
Ming-Ying Lu
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Chung-Feng Huang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Ming-Lun Yeh
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Chia-Yen Dai
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Jee-Fu Huang
Center for Cancer Research, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Wan-Long Chuang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Zu-Yau Lin
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Ming-Lung Yu
Center for Cancer Research, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Shu-Chi Wang
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Background: A large amount of epidemiological evidence indicates that persistent HCV infection is the main risk factor for HCC. We aimed to study the effects of persistent HCV infection on the interaction of the virus and host cell to identify cancer gene profiles. Methods: Next-generation sequencing (NGS) was used to identify differentially expressed genes between uninfected Huh7.5.1 control cells, short-term HCV (S-HCV), early long-term HCV (eL-HCV), and long-term HCV (L-HCV) infections, which were analyzed using different dynamic bioinformatics and analytic tools. mRNA expression was validated and quantified using q-PCR. One hundred ninety-six serum samples of HCV patients with IFN/RBV treatment were used to study chemokine levels. Results: S-HCV activates an inflammatory response and drives cell death and apoptosis through cell cycle arrest via MAPK signaling. L-HCV promotes cell growth and alters cell adhesion and chemokine signaling via CXCL8-mediated-SRC regulation. A total of 196 serum samples from the HCV and HCV-HCC cohorts demonstrated significantly upregulated pro-inflammatory CXCL8 in non-SVR (persistent HCV infection) patients in the HCV-HCC group. Conclusions: Persistent infection with HCV induced pro-inflammatory CXCL8 and the oncogene SRC, thereby triggering and promoting hepatocarcinogenesis. CXCL8 may be a potential biomarker for monitoring HCV-related HCC progression.
