Liver regeneration accelerates hepatitis B virus‐related tumorigenesis of hepatocellular carcinoma

Molecular Oncology

Ih‐Jen Su¹  Hong‐Yi Chang¹  Hung‐Wen Tsai²  Yih‐Jyh Lin³  Chiao‐Fang Teng⁴  Wen‐Chuan Hsieh⁵  Yu‐Hao Kuo⁶ 

[1] Department of Biotechnology Southern Taiwan University of Science and Technology Tainan Taiwan;Department of Pathology National Cheng Kung University Hospital Tainan Taiwan;Division of General and Transplant Surgery Department of Surgery National Cheng Kung University Hospital Tainan Taiwan;Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan;National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Tainan Taiwan;Organ Transplantation Center China Medical University Hospital Taichung Taiwan;

关键词: hepatitis B virus;    hepatocellular carcinoma;    liver regeneration;    partial hepatectomy;   

DOI  :  10.1002/1878-0261.12318

来源: DOAJ

【 摘 要 】

Although partial hepatectomy (PH) to remove tumors provides a potential cure of hepatocellular carcinoma (HCC), long‐term survival of hepatitis B virus (HBV)‐related HCC patients after PH remains a big challenge. Early recurrence within 2 years post‐PH is associated with the dissemination of primary HCC. However, late recurrence after 2 years post‐PH is supposed due to the de novo or a secondary tumor. Since PH initiates liver regeneration (LR), we hypothesize that LR may accelerate tumorigenesis through activation of pre‐existing precancerous lesions in the remaining liver. In this study, we explored the potential role of several LR‐related factors in the de novo recurrence in a HBV X protein (HBx) transgenic mouse model receiving PH to mimic human HCC development. Following PH, we observed that tumor development was significantly accelerated from 16.9 to 10.4 months in HBx transgenic mice. The expression of suppressor of cytokine signaling (SOCS) family proteins was remarkably suppressed in livers of HBx transgenic relative to non‐transgenic mice from early to late stages after PH as compared with non‐PH mice. The expression of transforming growth factor‐β (TGF‐β)/Smad pathway, hepatocyte growth factor (HGF), Myc, signal transducer and activator of transcription 3 (STAT3), and β‐Catenin also showed a significant difference between livers of HBx transgenic and non‐transgenic mice at variable time points after PH in comparison with non‐PH mice. Taken together, our results provide an explanation for the high de novo recurrence of HBV‐related HCC after PH, probably through induction of the sequential changes of LR‐related SOCS family proteins, growth factors, and transcription factors, which may promote growth on the precancerous remnant liver.

【 授权许可】

Unknown