{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T22:22:27Z","timestamp":1776896547524,"version":"3.51.2"},"reference-count":67,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T00:00:00Z","timestamp":1581292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2221-E-037-003"],"award-info":[{"award-number":["MOST 108-2221-E-037-003"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI-108A1-MRCO-0419192"],"award-info":[{"award-number":["NHRI-108A1-MRCO-0419192"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"publisher","award":["NSYSUKMU107-P015"],"award-info":[{"award-number":["NSYSUKMU107-P015"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"publisher","award":["KMU-TC108A04"],"award-info":[{"award-number":["KMU-TC108A04"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001869","name":"Academia Sinica","doi-asserted-by":"publisher","award":["AS-KPQ-105-TPP"],"award-info":[{"award-number":["AS-KPQ-105-TPP"]}],"id":[{"id":"10.13039\/501100001869","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is among the ten most commonly diagnosed cancers and the fourth leading cause of cancer-related death. Patients with hepatitis B virus (HBV) infection are prone to developing chronic liver diseases (i.e., fibrosis and cirrhosis), and the HBV X antigen plays an important role in the development of HCC. The difficulty in detecting HCC at the early stages is one of the main reasons that the death rate approximates the incidence rate. The regulators controlling the downstream liver protein expression from HBV infection are unclear. Mass spectrometric techniques and customized programs were used to identify differentially expressed proteins which may be involved in the development of liver fibrosis and HCC progression in hepatitis B virus X protein transgenic mice (HBx mice). FSTL1, CTSB, and TGF-\u03b2 enhanced the signaling pathway proteins during the pathogenesis of HBx. Missing proteins can be essential in cell growth, differentiation, apoptosis, migration, metastasis or angiogenesis. We found that LHX2, BMP-5 and GDF11 had complex interactions with other missing proteins and BMP-5 had both tumor suppressing and tumorigenic roles. BMP-5 may be involved in fibrosis and tumorigenic processes in the liver. These results provide us an understanding of the mechanism of HBx-induced disorders, and may serve as molecular targets for liver treatment.<\/jats:p>","DOI":"10.3390\/cancers12020409","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T11:45:30Z","timestamp":1581421530000},"page":"409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Utilizing Experimental Mouse Model to Identify Effectors of Hepatocellular Carcinoma Induced by HBx Antigen"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-0498","authenticated-orcid":false,"given":"Ming-Hui","family":"Yang","sequence":"first","affiliation":[{"name":"National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli 350, Taiwan"},{"name":"Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Mackay Memorial Hospital, Taipei 104, Taiwan"},{"name":"Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing and Management, Taipei 112, Taiwan"},{"name":"School of Medicine, Mackay Medical College, New Taipei City 252, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao-Hsuan","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-3581","authenticated-orcid":false,"given":"Wan-Chi","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin-Chuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Nuclear Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ko-Chin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0722-0201","authenticated-orcid":false,"given":"Hsin-Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Instrumentation Center, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Hui","family":"Yuan","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Department of Chemistry, National University of Singapore, Singapore 119077, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-3862","authenticated-orcid":false,"given":"Che-Hsin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Science, National Sun Yat-sen University, Kaohsiung 804, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ming Arthur","family":"Chen","sequence":"additional","affiliation":[{"name":"Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1917-5893","authenticated-orcid":false,"given":"Yu-Chang","family":"Tyan","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 804, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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