{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:18:15Z","timestamp":1791487095222,"version":"4.3.4"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Backgrounds and Aims<\/jats:title>\n                    <jats:p>Structural dynamics of basement membrane components are still to be elucidated in the process of hepatocarcinogenesis. We evaluated the characteristics of HCC expressing laminin \u03b32 monomer (LG2m), a basement membrane component not detected in normal tissues, for HCC diagnosis. We further determined whether elevated serum LG2m is a risk factor for HCC development in patients with chronic hepatitis C (CHC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      In HCC cell lines, LG2m was expressed in alpha\u2010fetoprotein (AFP)\u2010negative, CD90\u2010positive cells characterized by highly metastatic natures. Using 14 cell lines and 258 HCC microarray data, we identified that LG2m gene signature was associated with Hoshida\u2019s S1\/Boyault\u2019s G3 molecular subclasses with poor prognosis, which could not be recognized by AFP. Serum LG2m was assessed in 24 healthy donors, 133 chronic liver disease patients, and 142 HCC patients, and sensitivity and specificity of LG2m testing for HCC diagnosis were 62.9% and 70.5%, respectively (cutoff, 30\u00a0pg\/mL). We evaluated the consequence of LG2m elevation in two independent HCC cohorts (n\u00a0=\u00a047 and n\u00a0=\u00a081), and LG2m\u2010high HCC showed poor prognosis with later development of distant organ metastasis (cutoff, 60\u00a0pg\/mL). LG2m was slightly elevated in a subset of CHC patients, and Kaplan\u2010Meier analysis indicated a high incidence of HCC (n\u00a0=\u00a070). For validation, we enrolled 399 CHC patients with sustained virological response (SVR) as a multicenter, prospective study, and serum LG2m elevation correlated with a high incidence of HCC in the CHC patients with SVR (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LG2m is a predictive biomarker for the development of metastatic HCC. Elevated serum LG2m is an HCC risk in CHC patients who have achieved SVR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31758","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T23:14:13Z","timestamp":1613862853000},"page":"760-775","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Serum Laminin \u03b32 Monomer as a Diagnostic and Predictive Biomarker for Hepatocellular Carcinoma"],"prefix":"10.1097","volume":"74","author":[{"given":"Taro","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of General Medicine,Kanazawa University Hospital,Kanazawa,Japan"},{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiko","family":"Koshikawa","sequence":"additional","affiliation":[{"name":"Division of Cancer Cell Research,Kanagawa Cancer Center Research Institute,Yokohama,Japan"},{"name":"Institute of Medical Science,The University of Tokyo,Tokyo,Japan"},{"name":"Department of Life Science and Technology,Tokyo Institute of Technology,Yokohama,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Shimakami","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Terashima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Diagnostics Division,Abbott Japan LLC,Matsudo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouki","family":"Nio","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Horii","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriho","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniaki","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eishiro","family":"Mizukoshi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Kitao","sequence":"additional","affiliation":[{"name":"Department of Radiology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Radiology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuko","family":"Takahara","sequence":"additional","affiliation":[{"name":"Innovative Clinical Research Center,Kanazawa University,Kanazawa, Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Imai","sequence":"additional","affiliation":[{"name":"Innovative Clinical Research Center,Kanazawa University,Kanazawa, Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Innovative Clinical Research Center,Kanazawa University,Kanazawa, Kanazawa University Hospital,Kanazawa,Japan"},{"name":"Center for Integrated Medical Research,Hiroshima University Hospital,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Murayama","sequence":"additional","affiliation":[{"name":"Innovative Clinical Research Center,Kanazawa University,Kanazawa, Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunari","family":"Nakamoto","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine,University of Fukui School of Medical Sciences,Yoshida\u2010gun,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisaku","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Diagnostics Division,Abbott Japan LLC,Matsudo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Diagnostics Division,Abbott Japan LLC,Matsudo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoharu","family":"Seiki","sequence":"additional","affiliation":[{"name":"Faculty of Medicine,Institute of Medical,Pharmaceutical and Health Sciences,Kanazawa University,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Kanazawa University Hospital,Kanazawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"hep31758-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1056\/NEJMra1713263","article-title":"Hepatocellular carcinoma","volume":"380","year":"2019","journal-title":"N Engl J Med"},{"key":"hep31758-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/liv.12965","article-title":"Early diagnosis of liver cancer: an appraisal of international recommendations and future perspectives","volume":"36","year":"2016","journal-title":"Liver Int"},{"key":"hep31758-bib-0003-20250824","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1158\/0008-5472.CAN-09-1089","article-title":"Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma","volume":"69","year":"2009","journal-title":"Cancer Res"},{"key":"hep31758-bib-0004-20250824","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/hep.21467","article-title":"Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets","volume":"45","year":"2007","journal-title":"Hepatology"},{"key":"hep31758-bib-0005-20250824","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1002\/hep.27093","article-title":"Gd\u2010EOB\u2010DTPA\u2010enhanced magnetic resonance imaging and alpha\u2010fetoprotein predict prognosis of early\u2010stage hepatocellular carcinoma","volume":"60","year":"2014","journal-title":"Hepatology"},{"key":"hep31758-bib-0006-20250824","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/nrgastro.2016.176","article-title":"Global epidemiology and burden of HCV infection and HCV\u2010related disease","volume":"14","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep31758-bib-0007-20250824","first-page":"S58","article-title":"Natural history of hepatitis C","volume":"61(1 Suppl.)","year":"2014","journal-title":"J Hepatol"},{"issue":"Suppl. 1","key":"hep31758-bib-0008-20250824","first-page":"7","article-title":"Treatment of hepatitis C virus infection with direct\u2010acting antiviral agents: 100% cure?","volume":"38","year":"2018","journal-title":"Liver Int"},{"key":"hep31758-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(18)32111-1","article-title":"Clinical outcomes in patients with chronic hepatitis C after direct\u2010acting antiviral treatment: a prospective cohort study","volume":"393","year":"2019","journal-title":"Lancet"},{"key":"hep31758-bib-0010-20250824","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1053\/j.gastro.2018.10.033","article-title":"What are the benefits of a sustained virologic response to direct\u2010acting antiviral therapy for hepatitis C virus infection?","volume":"156","year":"2019","journal-title":"Gastroenterology"},{"key":"hep31758-bib-0011-20250824","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1053\/j.gastro.2017.06.012","article-title":"Risk of hepatocellular cancer in HCV patients treated with direct\u2010acting antiviral agents","volume":"153","year":"2017","journal-title":"Gastroenterology"},{"issue":"Suppl. 1","key":"hep31758-bib-0012-20250824","first-page":"139","article-title":"The impact of treatment of hepatitis C with DAAs on the occurrence of HCC","volume":"38","year":"2018","journal-title":"Liver Int"},{"key":"hep31758-bib-0013-20250824","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/hep.29913","article-title":"Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases","volume":"68","year":"2018","journal-title":"Hepatology"},{"key":"hep31758-bib-0015-20250824","first-page":"5596","article-title":"Overexpression of laminin gamma2 chain monomer in invading gastric carcinoma cells","volume":"59","year":"1999","journal-title":"Cancer Res"},{"key":"hep31758-bib-0016-20250824","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1111\/cas.13261","article-title":"Serum monomeric laminin\u2010gamma2 as a novel biomarker for hepatocellular carcinoma","volume":"108","year":"2017","journal-title":"Cancer Sci"},{"key":"hep31758-bib-0017-20250824","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1158\/0008-5472.CAN-07-5269","article-title":"Development of a new tracking tool for the human monomeric laminin\u2010gamma 2 chain in vitro and in vivo","volume":"68","year":"2008","journal-title":"Cancer Res"},{"key":"hep31758-bib-0018-20250824","first-page":"98","article-title":"Establishment and characterization of a human hepatocellular carcinoma cell line JHH\u20104","volume":"1","year":"1988","journal-title":"Hum Cell"},{"key":"hep31758-bib-0019-20250824","first-page":"152","article-title":"Establishment and characterization of a human hepatocellular carcinoma cell line JHH\u20107 producing alpha\u2010fetoprotein and carcinoembryonic antigen\u2014changes in secretion of AFP and CEA from JHH\u20107 cells after heat treatment","volume":"3","year":"1990","journal-title":"Hum Cell"},{"key":"hep31758-bib-0020-20250824","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1002\/hep.26168","article-title":"Discrete nature of EpCAM(+) and CD90(+) cancer stem cells in human hepatocellular carcinoma","volume":"57","year":"2013","journal-title":"Hepatology"},{"key":"hep31758-bib-0021-20250824","article-title":"Evidence\u2010based clinical practice guidelines for hepatocellular carcinoma. The Japan Society of Hepatology 2013 update (3rd JSH\u2010HCC Guidelines)","volume":"45","year":"2015","journal-title":"Hepatol Res"},{"key":"hep31758-bib-0022-20250824","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1053\/j.gastro.2011.02.006","article-title":"Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma","volume":"140","year":"2011","journal-title":"Gastroenterology"},{"key":"hep31758-bib-0023-20250824","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1172\/JCI66024","article-title":"Cancer stem cells in the development of liver cancer","volume":"123","year":"2013","journal-title":"J Clin Invest"},{"key":"hep31758-bib-0024-20250824","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1158\/0008-5472.CAN-07-6013","article-title":"EpCAM and alpha\u2010fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma","volume":"68","year":"2008","journal-title":"Cancer Res"},{"key":"hep31758-bib-0025-20250824","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1053\/j.gastro.2008.12.004","article-title":"EpCAM\u2010positive hepatocellular carcinoma cells are tumor\u2010initiating cells with stem\/progenitor cell features","volume":"136","year":"2009","journal-title":"Gastroenterology"},{"key":"hep31758-bib-0026-20250824","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s00535-014-0951-1","article-title":"Orchestration of hepatocellular carcinoma development by diverse liver cancer stem cells","volume":"49","year":"2014","journal-title":"J Gastroenterol"},{"key":"hep31758-bib-0027-20250824","doi-asserted-by":"crossref","first-page":"33940","DOI":"10.1074\/jbc.M110.136044","article-title":"ZEB1 coordinately regulates laminin\u2010332 and {beta}4 integrin expression altering the invasive phenotype of prostate cancer cells","volume":"285","year":"2010","journal-title":"J Biol Chem"},{"key":"hep31758-bib-0028-20250824","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/cdd.2014.228","article-title":"LAMC2 enhances the metastatic potential of lung adenocarcinoma","volume":"22","year":"2015","journal-title":"Cell Death Differ"},{"key":"hep31758-bib-0029-20250824","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.ajpath.2019.03.012","article-title":"Silencing of LAMC2 reverses epithelial\u2010mesenchymal transition and inhibits angiogenesis in cholangiocarcinoma via inactivation of the epidermal growth factor receptor signaling pathway","volume":"189","year":"2019","journal-title":"Am J Pathol"},{"key":"hep31758-bib-0030-20250824","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.jhep.2015.11.011","article-title":"Laminin\u2010332 sustains chemoresistance and quiescence as part of the human hepatic cancer stem cell niche","volume":"64","year":"2016","journal-title":"J Hepatol"},{"key":"hep31758-bib-0031-20250824","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","year":"2011","journal-title":"Cell"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.31758","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.31758","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.31758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T23:10:43Z","timestamp":1756077043000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.31758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,28]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.31758","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,28]]},"assertion":[{"value":"2020-06-19","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-11","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}