{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T20:05:47Z","timestamp":1781121947496,"version":"3.54.1"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR-107-034"],"award-info":[{"award-number":["DMR-107-034"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107-2320-B-039-053"],"award-info":[{"award-number":["MOST 107-2320-B-039-053"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner.<\/jats:p>","DOI":"10.3390\/v12080796","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T09:06:09Z","timestamp":1595581569000},"page":"796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Next-Generation Sequencing-Based Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma Predicts Hepatocellular Carcinoma Recurrence"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-0571","authenticated-orcid":false,"given":"Chiao-Fang","family":"Teng","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, No.91, Hsueh-Shih Rd., Northern Dist., Taichung City 404, Taiwan"},{"name":"Organ Transplantation Center, China Medical University Hospital, No.2, Yude Rd., Northern Dist., Taichung City 404, Taiwan"},{"name":"Research Center for Cancer Biology, China Medical University, Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-7462","authenticated-orcid":false,"given":"Tsai-Chung","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Public Health, China Medical University, Taichung City 404, Taiwan"},{"name":"Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung City 413, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsi-Yuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, China Medical University Hospital, Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, No.91, Hsueh-Shih Rd., Northern Dist., Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Shu","family":"Chen","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, China Medical University Hospital, No.2, Yude Rd., Northern Dist., Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woei-Cherng","family":"Shyu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, No.91, Hsueh-Shih Rd., Northern Dist., Taichung City 404, Taiwan"},{"name":"Department of Occupational Therapy, Asia University, Taichung City 413, Taiwan"},{"name":"Department of Neurology, China Medical University Hospital, Taichung City 404, Taiwan"},{"name":"Translational Medicine Research Center, China Medical University Hospital, Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2638-7883","authenticated-orcid":false,"given":"Han-Chieh","family":"Wu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-6086","authenticated-orcid":false,"given":"Cheng-Yuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung City 404, Taiwan"},{"name":"School of Medicine, China Medical University, Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ih-Jen","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Southern Taiwan University of Science and Technology, No.1, Nantai St., Yongkang Dist., Tainan City 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Bin","family":"Jeng","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, China Medical University Hospital, No.2, Yude Rd., Northern Dist., Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16019","DOI":"10.1038\/nrdp.2016.19","article-title":"Hepatocellular carcinoma","volume":"2","author":"Llovet","year":"2016","journal-title":"Nat. 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