The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery
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 prote...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/10/5376 |
| _version_ | 1797499269911937024 |
|---|---|
| author | Hung-Wen Tsai Yun-Ping Lee Chia-Jui Yen Kuang-Hsiung Cheng Chien-Jung Huang Wenya Huang |
| author_facet | Hung-Wen Tsai Yun-Ping Lee Chia-Jui Yen Kuang-Hsiung Cheng Chien-Jung Huang Wenya Huang |
| author_sort | Hung-Wen Tsai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:45:03Z |
| format | Article |
| id | doaj.art-09151fe30f174f05b27afde45c3c4c15 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:45:03Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-09151fe30f174f05b27afde45c3c4c152023-11-23T11:21:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310537610.3390/ijms23105376The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative SurgeryHung-Wen Tsai0Yun-Ping Lee1Chia-Jui Yen2Kuang-Hsiung Cheng3Chien-Jung Huang4Wenya Huang5Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Internal Medicine, Taipei City Hospital, Taipei 10341, TaiwanDepartment of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanChronic 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.https://www.mdpi.com/1422-0067/23/10/5376chronic hepatitis BHBV surface antigenELISAhepatocellular carcinomaprognosis |
| spellingShingle | Hung-Wen Tsai Yun-Ping Lee Chia-Jui Yen Kuang-Hsiung Cheng Chien-Jung Huang Wenya Huang The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery International Journal of Molecular Sciences chronic hepatitis B HBV surface antigen ELISA hepatocellular carcinoma prognosis |
| title | The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery |
| title_full | The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery |
| title_fullStr | The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery |
| title_full_unstemmed | The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery |
| title_short | The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery |
| title_sort | serum hepatitis b virus large surface protein as high risk recurrence biomarker for hepatoma after curative surgery |
| topic | chronic hepatitis B HBV surface antigen ELISA hepatocellular carcinoma prognosis |
| url | https://www.mdpi.com/1422-0067/23/10/5376 |
| work_keys_str_mv | AT hungwentsai theserumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT yunpinglee theserumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT chiajuiyen theserumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT kuanghsiungcheng theserumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT chienjunghuang theserumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT wenyahuang theserumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT hungwentsai serumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT yunpinglee serumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT chiajuiyen serumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT kuanghsiungcheng serumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT chienjunghuang serumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery AT wenyahuang serumhepatitisbviruslargesurfaceproteinashighriskrecurrencebiomarkerforhepatomaaftercurativesurgery |