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Article

The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery

1
Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
2
Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
3
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
4
Department of Internal Medicine, Taipei City Hospital, Taipei 10341, Taiwan
5
Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editors: Cristian Turato and Stefania Cannito
Int. J. Mol. Sci. 2022, 23(10), 5376; https://doi.org/10.3390/ijms23105376
Received: 13 April 2022 / Revised: 9 May 2022 / Accepted: 9 May 2022 / Published: 11 May 2022
Chronic hepatitis B (CHB) virus infection is the most important cause of HCC and is also associated with tumor progression. The development of viral biomarkers for HCC prognosis is critical in evaluating relative risks to recurrence in the CHB HCC patients. We report that the large HBV surface protein (LHBS) expression increased in the tumors, implicating that it played a significant role in tumor development. To detect the LHBS in serum and evaluate its association with HCC progression, we developed a sandwich ELISA method for LHBS. The mouse monoclonal antibodies for the pre-S1, pre-S2, and HBS regions were in-house generated and constructed into a chemiluminescent sandwich ELISA system, which allowed sensitive and quantitative measurement of the protein. Using this ELISA assay, we estimated the expression of LHBS in CHB and HCC patients. We found that the serum LHBS level was correlated with the HBS but not the viral titer in serum, indicating that HBV surface proteins’ expression does not mainly depend on viral replication. Moreover, both serum LHBS and HBS levels were lower in the HCC patients than in the CHB. The liver LHBS signals, detected by immunohistochemical staining, showed significant correlations with the serum LHBS and HBS levels. In addition, the more elevated serum LHBS but not HBS level was significantly associated with cirrhosis and worse disease-free and overall survival rates, based on the multivariate analysis. Conclusion: LHBS plays a specific role in tumor progression and is an independent parameter associated with HCC recurrence. Serum LHBS represents a novel noninvasive biomarker for HCC patients with a worse prognosis after surgery. View Full-Text
Keywords: chronic hepatitis B; HBV surface antigen; ELISA; hepatocellular carcinoma; prognosis chronic hepatitis B; HBV surface antigen; ELISA; hepatocellular carcinoma; prognosis
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MDPI and ACS Style

Tsai, H.-W.; Lee, Y.-P.; Yen, C.-J.; Cheng, K.-H.; Huang, C.-J.; Huang, W. The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery. Int. J. Mol. Sci. 2022, 23, 5376. https://doi.org/10.3390/ijms23105376

AMA Style

Tsai H-W, Lee Y-P, Yen C-J, Cheng K-H, Huang C-J, Huang W. The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery. International Journal of Molecular Sciences. 2022; 23(10):5376. https://doi.org/10.3390/ijms23105376

Chicago/Turabian Style

Tsai, Hung-Wen, Yun-Ping Lee, Chia-Jui Yen, Kuang-Hsiung Cheng, Chien-Jung Huang, and Wenya Huang. 2022. "The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery" International Journal of Molecular Sciences 23, no. 10: 5376. https://doi.org/10.3390/ijms23105376

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