{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T19:20:55Z","timestamp":1781551255360,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Medical University Hospital, Taiwan","award":["DMR-111-046"],"award-info":[{"award-number":["DMR-111-046"]}]}],"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 and is closely associated with chronic hepatitis B virus (HBV) infection. Pre-S deleted proteins are naturally occurring mutant forms of HBV large surface proteins that are expressed by HBV surface genes harboring deletion mutations over the pre-S gene segments. It has been well demonstrated that HBV pre-S deleted proteins function as important oncoproteins, which promote malignant phenotypes of hepatocytes through the activation of multiple oncogenic signaling pathways and result in HCC formation. The oncogenic signaling pathways activated by pre-S deleted proteins have been verified as potential therapeutic targets for the prevention of HCC development. Moreover, the presence of pre-S gene deletions and the expression of pre-S deleted proteins in the blood and liver tissues of HBV-infected patients have been evaluated as valuable biomarkers for predicting a higher risk of HCC development and recurrence after curative surgical resection. Therefore, the precise detection of pre-S gene deletions and pre-S deleted proteins holds great promise as regards identifying the patients at higher risk of HCC development and recurrence, thus aiding in more timely and better treatments to improve their survival. This review summarizes the major approaches used for the detection of pre-S gene deletions and pre-S deleted proteins, including the approaches based on Sanger DNA sequencing, pre-S gene chips, next-generation sequencing and immunohistochemistry staining, and it highlights their important applications in the prediction of higher risks of HCC development and recurrence.<\/jats:p>","DOI":"10.3390\/v14020428","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:23:29Z","timestamp":1645431809000},"page":"428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Approaches for Detection of Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins and Their Application in Prediction of Higher Risk of Hepatocellular Carcinoma Development and Recurrence"],"prefix":"10.3390","volume":"14","author":[{"given":"Yueh-Te","family":"Lin","sequence":"first","affiliation":[{"name":"Cancer Genome Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Bin","family":"Jeng","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, China Medical University Hospital, Taichung 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, Tainan 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-0571","authenticated-orcid":false,"given":"Chiao-Fang","family":"Teng","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan"},{"name":"Research Center for Cancer Biology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16018","DOI":"10.1038\/nrdp.2016.18","article-title":"Hepatocellular carcinoma","volume":"2","author":"Llovet","year":"2016","journal-title":"Nat. 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