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

Chiao Fang Teng, Hong Yi Chang, Hung-Wen Tsai, Wen Chuan Hsieh, Yu Hao Kuo, Ih Jen Su, Yih-Jyh Lin

研究成果: Article

2 引文 (Scopus)

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.

原文English
頁(從 - 到)1175-1187
頁數13
期刊Molecular Oncology
12
發行號7
DOIs
出版狀態Published - 2018 六月 1

指紋

Liver Regeneration
Hepatectomy
Hepatitis B virus
Hepatocellular Carcinoma
Carcinogenesis
Suppressor of Cytokine Signaling Proteins
Recurrence
Liver
Transgenic Mice
Catenins
STAT3 Transcription Factor
Neoplasms
Hepatocyte Growth Factor
Transforming Growth Factors
Intercellular Signaling Peptides and Proteins
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

引用此文

Teng, Chiao Fang ; Chang, Hong Yi ; Tsai, Hung-Wen ; Hsieh, Wen Chuan ; Kuo, Yu Hao ; Su, Ih Jen ; Lin, Yih-Jyh. / Liver regeneration accelerates hepatitis B virus-related tumorigenesis of hepatocellular carcinoma. 於: Molecular Oncology. 2018 ; 卷 12, 編號 7. 頁 1175-1187.
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abstract = "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.",
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Liver regeneration accelerates hepatitis B virus-related tumorigenesis of hepatocellular carcinoma. / Teng, Chiao Fang; Chang, Hong Yi; Tsai, Hung-Wen; Hsieh, Wen Chuan; Kuo, Yu Hao; Su, Ih Jen; Lin, Yih-Jyh.

於: Molecular Oncology, 卷 12, 編號 7, 01.06.2018, p. 1175-1187.

研究成果: Article

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AU - Hsieh, Wen Chuan

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AU - Su, Ih Jen

AU - Lin, Yih-Jyh

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AB - 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.

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