{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:19:41Z","timestamp":1785251981752,"version":"3.55.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T00:00:00Z","timestamp":1491350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T00:00:00Z","timestamp":1491350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatoblastoma (HB) is the most common primary liver cancer in children. The conventional serum marker for HB, alpha-fetoprotein (AFP), has its limitations. Novel serum markers need to be explored. Glypican 3 (GPC3) has been reported to be an excellent histological immunomarker for HB. However, the clinical value of serum GPC3 in patients with HB is unknown. A total of 184 serum samples were tested for both GPC3 by ELISA, and AFP by immunometric assay. Of these, 134 were from 32 patients with HB at three treatment stages, 30 from age-matched patients with benign hepatobiliary disorders (BHD) and 20 from age-matched \u201cnormal controls\u201d(NC). We found that the GPC3 levels in HB pretreatment group were significantly higher than those in NC group and HB remission group but not statistically different from those in BHD group and HB during treatment group. In contrast, AFP showed significant differences among different groups. The areas under the receiver operating curve (AUROC) value, sensitivity and specificity of GPC3 for HB pretreatment group versus all controls were all significantly lower than those of AFP. Serum GPC3 levels were not associated with prognostic parameters. We concluded that GPC3 is inferior to AFP as a serum marker for HB.<\/jats:p>","DOI":"10.1038\/srep45932","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T11:34:58Z","timestamp":1491392098000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Glypican 3 as a Serum Marker for Hepatoblastoma"],"prefix":"10.1038","volume":"7","author":[{"given":"Shengmei","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice R. G.","family":"O\u2019Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Andresen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,5]]},"reference":[{"key":"BFsrep45932_CR1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.5858\/2007-131-520-PFTEOS","volume":"131","author":"MJ Finegold","year":"2007","unstructured":"Finegold, M. J., Lopez-Terrada, D. H., Bowen, J., Washington, M. K. & Qualman, S. J. Protocol for the examination of specimens from pediatric patients with hepatoblastoma. Archives of pathology & laboratory medicine 131, 520\u2013529 (2007).","journal-title":"Archives of pathology & laboratory medicine"},{"key":"BFsrep45932_CR2","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1002\/pbc.24219","volume":"59","author":"AD Trobaugh-Lotrario","year":"2012","unstructured":"Trobaugh-Lotrario, A. D. & Katzenstein, H. M. Chemotherapeutic approaches for newly diagnosed hepatoblastoma: past, present, and future strategies. Pediatric blood & cancer 59, 809\u2013812 (2012).","journal-title":"Pediatric blood & cancer"},{"key":"BFsrep45932_CR3","doi-asserted-by":"publisher","first-page":"3301","DOI":"10.1200\/JCO.2010.29.3837","volume":"29","author":"MH Malogolowkin","year":"2011","unstructured":"Malogolowkin, M. H. et al. Complete surgical resection is curative for children with hepatoblastoma with pure fetal histology: a report from the Children\u2019s Oncology Group. Journal of clinical oncology 29, 3301\u20133306 (2011).","journal-title":"Journal of clinical oncology"},{"key":"BFsrep45932_CR4","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.jpeds.2004.09.011","volume":"146","author":"GM Tiao","year":"2005","unstructured":"Tiao, G. M. et al. The current management of hepatoblastoma: a combination of chemotherapy, conventional resection, and liver transplantation. The Journal of pediatrics 146, 204\u2013211 (2005).","journal-title":"The Journal of pediatrics"},{"key":"BFsrep45932_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00383-010-2708-0","volume":"27","author":"T Hishiki","year":"2011","unstructured":"Hishiki, T. et al. Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT. Pediatric surgery international 27, 1\u20138 (2011).","journal-title":"Pediatric surgery international"},{"key":"BFsrep45932_CR6","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.ejca.2003.06.003","volume":"40","author":"G Perilongo","year":"2004","unstructured":"Perilongo, G. et al. Risk-adapted treatment for childhood hepatoblastoma. final report of the second study of the International Society of Paediatric Oncology--SIOPEL 2. Eur J Cancer 40, 411\u2013421 (2004).","journal-title":"Eur J Cancer"},{"key":"BFsrep45932_CR7","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1053\/j.sempedsurg.2011.10.011","volume":"21","author":"D von Schweinitz","year":"2012","unstructured":"von Schweinitz, D. Hepatoblastoma: recent developments in research and treatment. Seminars in pediatric surgery 21, 21\u201330 (2012).","journal-title":"Seminars in pediatric surgery"},{"key":"BFsrep45932_CR8","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3109\/08880019809167228","volume":"15","author":"ME Blohm","year":"1998","unstructured":"Blohm, M. E., Vesterling-Horner, D., Calaminus, G. & Gobel, U. Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age. Pediatric hematology and oncology 15, 135\u2013142 (1998).","journal-title":"Pediatric hematology and oncology"},{"key":"BFsrep45932_CR9","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1203\/00006450-198101000-00012","volume":"15","author":"JT Wu","year":"1981","unstructured":"Wu, J. T., Book, L. & Sudar, K. Serum alpha fetoprotein (AFP) levels in normal infants. Pediatric research 15, 50\u201352 (1981).","journal-title":"Pediatric research"},{"key":"BFsrep45932_CR10","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1080\/08880010600954397","volume":"23","author":"N Sari","year":"2006","unstructured":"Sari, N., Yalcin, B., Akyuz, C., Haliloglu, M. & Buyukpamukcu, M. Infantile hepatic hemangioendothelioma with elevated serum alpha-fetoprotein. Pediatric hematology and oncology 23, 639\u2013647 (2006).","journal-title":"Pediatric hematology and oncology"},{"key":"BFsrep45932_CR11","first-page":"1423","volume":"55","author":"CH Chen","year":"2008","unstructured":"Chen, C. H., Lin, S. T., Kuo, C. L. & Nien, C. K. Clinical significance of elevated alpha-fetoprotein (AFP) in chronic hepatitis C without hepatocellular carcinoma. Hepato-gastroenterology 55, 1423\u20131427 (2008).","journal-title":"Hepato-gastroenterology"},{"key":"BFsrep45932_CR12","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.ejca.2007.11.022","volume":"44","author":"M De Ioris","year":"2008","unstructured":"De Ioris, M. et al. Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: the SIOPEL group experience. Eur J Cancer 44, 545\u2013550 (2008).","journal-title":"Eur J Cancer"},{"key":"BFsrep45932_CR13","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1002\/hep.21328","volume":"44","author":"JH Luo","year":"2006","unstructured":"Luo, J. H. et al. Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology 44, 1012\u20131024 (2006).","journal-title":"Hepatology"},{"key":"BFsrep45932_CR14","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1136\/jcp.2010.075374","volume":"63","author":"FH Wang","year":"2010","unstructured":"Wang, F. H. et al. Diagnostic utility of glypican-3 for hepatocellular carcinoma on liver needle biopsy. Journal of clinical pathology 63, 599\u2013603 (2010).","journal-title":"Journal of clinical pathology"},{"key":"BFsrep45932_CR15","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1111\/his.12730","volume":"67","author":"S Zhou","year":"2015","unstructured":"Zhou, S., Parham, D. M., Yung, E., Pattengale, P. & Wang, L. Quantification of glypican 3, beta-catenin and claudin-1 protein expression in hepatoblastoma and paediatric hepatocellular carcinoma by colour deconvolution. Histopathology 67, 905\u2013913 (2015).","journal-title":"Histopathology"},{"key":"BFsrep45932_CR16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0016-5085(03)00689-9","volume":"125","author":"M Capurro","year":"2003","unstructured":"Capurro, M. et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 125, 89\u201397 (2003).","journal-title":"Gastroenterology"},{"key":"BFsrep45932_CR17","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1158\/0008-5472.CAN-03-2191","volume":"64","author":"Y Hippo","year":"2004","unstructured":"Hippo, Y. et al. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer research 64, 2418\u20132423 (2004).","journal-title":"Cancer research"},{"key":"BFsrep45932_CR18","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/S0006-291X(03)00908-2","volume":"306","author":"T Nakatsura","year":"2003","unstructured":"Nakatsura, T. et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochemical and biophysical research communications 306, 16\u201325 (2003).","journal-title":"Biochemical and biophysical research communications"},{"key":"BFsrep45932_CR19","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1177\/1533034615605248","volume":"15","author":"X Jia","year":"2015","unstructured":"Jia, X. et al. Assessment of the Clinical Utility of Glypican 3 as a Serum Marker for the Diagnosis of Hepatocellular Carcinoma. Technology in cancer research & treatment 15, 780\u2013786 (2015).","journal-title":"Technology in cancer research & treatment"},{"key":"BFsrep45932_CR20","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.1074\/jbc.M410090200","volume":"280","author":"HH Song","year":"2005","unstructured":"Song, H. H., Shi, W., Xiang, Y. Y. & Filmus, J. The loss of glypican-3 induces alterations in Wnt signaling. The Journal of biological chemistry 280, 2116\u20132125 (2005).","journal-title":"The Journal of biological chemistry"},{"key":"BFsrep45932_CR21","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.devcel.2008.03.006","volume":"14","author":"MI Capurro","year":"2008","unstructured":"Capurro, M. I. et al. Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding. Developmental cell 14, 700\u2013711 (2008).","journal-title":"Developmental cell"},{"key":"BFsrep45932_CR22","doi-asserted-by":"publisher","first-page":"7574","DOI":"10.1074\/jbc.272.12.7574","volume":"272","author":"HH Song","year":"1997","unstructured":"Song, H. H., Shi, W. & Filmus, J. OCI-5\/rat glypican-3 binds to fibroblast growth factor-2 but not to insulin-like growth factor-2. The Journal of biological chemistry 272, 7574\u20137577 (1997).","journal-title":"The Journal of biological chemistry"},{"key":"BFsrep45932_CR23","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1006\/dbio.2000.9831","volume":"225","author":"S Paine-Saunders","year":"2000","unstructured":"Paine-Saunders, S., Viviano, B. L., Zupicich, J., Skarnes, W. C. & Saunders, S. glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Developmental biology 225, 179\u2013187 (2000).","journal-title":"Developmental biology"},{"key":"BFsrep45932_CR24","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.humpath.2007.06.006","volume":"39","author":"DL Zynger","year":"2008","unstructured":"Zynger, D. L. et al. Expression of glypican 3 in hepatoblastoma: an immunohistochemical study of 65 cases. Human pathology 39, 224\u2013230 (2008).","journal-title":"Human pathology"},{"key":"BFsrep45932_CR25","first-page":"1718","volume":"58","author":"SS Qiao","year":"2011","unstructured":"Qiao, S. S. et al. Simultaneous measurements of serum AFP, GPC-3 and HCCR for diagnosing hepatocellular carcinoma. Hepato-gastroenterology 58, 1718\u20131724 (2011).","journal-title":"Hepato-gastroenterology"},{"key":"BFsrep45932_CR26","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/j.1440-1746.2009.05988.x","volume":"25","author":"P Tangkijvanich","year":"2010","unstructured":"Tangkijvanich, P. et al. Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers. Journal of gastroenterology and hepatology 25, 129\u2013137 (2010).","journal-title":"Journal of gastroenterology and hepatology"},{"key":"BFsrep45932_CR27","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1111\/j.1872-034X.2010.00624.x","volume":"40","author":"E Yasuda","year":"2010","unstructured":"Yasuda, E. et al. Evaluation for clinical utility of GPC3, measured by a commercially available ELISA kit with Glypican-3 (GPC3) antibody, as a serological and histological marker for hepatocellular carcinoma. Hepatology research 40, 477\u2013485 (2010).","journal-title":"Hepatology research"},{"key":"BFsrep45932_CR28","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/jcla.20484","volume":"25","author":"H Ozkan","year":"2011","unstructured":"Ozkan, H. et al. Diagnostic and prognostic role of serum glypican 3 in patients with hepatocellular carcinoma. Journal of clinical laboratory analysis 25, 350\u2013353 (2011).","journal-title":"Journal of clinical laboratory analysis"},{"key":"BFsrep45932_CR29","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1111\/jgh.12461","volume":"29","author":"Y Wang","year":"2014","unstructured":"Wang, Y. et al. Golgi protein 73, not Glypican-3, may be a tumor marker complementary to alpha-Fetoprotein for hepatocellular carcinoma diagnosis. Journal of gastroenterology and hepatology 29, 597\u2013602 (2014).","journal-title":"Journal of gastroenterology and hepatology"},{"key":"BFsrep45932_CR30","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/1471-2407","volume":"8","author":"G Beale","year":"2008","unstructured":"Beale, G. et al. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC cancer 8, 200, 10.1186\/1471-2407 (2008).","journal-title":"BMC cancer"},{"key":"BFsrep45932_CR31","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/cncr.10632","volume":"95","author":"J Fuchs","year":"2002","unstructured":"Fuchs, J. et al. Pretreatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Pediatric Liver Tumor Study HB 94. Cancer 95, 172\u2013182 (2002).","journal-title":"Cancer"},{"key":"BFsrep45932_CR32","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1002\/pbc.22088","volume":"53","author":"RL Meyers","year":"2009","unstructured":"Meyers, R. L. et al. Predictive power of pretreatment prognostic factors in children with hepatoblastoma: a report from the Children\u2019s Oncology Group. Pediatric blood & cancer 53, 1016\u20131022 (2009).","journal-title":"Pediatric blood & cancer"},{"key":"BFsrep45932_CR33","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1016\/j.ejca.2011.12.011","volume":"48","author":"R Maibach","year":"2012","unstructured":"Maibach, R. et al. Prognostic stratification for children with hepatoblastoma: the SIOPEL experience. Eur J Cancer 48, 1543\u20131549 (2012).","journal-title":"Eur J Cancer"},{"key":"BFsrep45932_CR34","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s11427-013-4451-y","volume":"56","author":"J Yu","year":"2013","unstructured":"Yu, J. et al. Clinical application of specific antibody against glypican-3 for hepatocellular carcinoma diagnosis. Science China. Life sciences 56, 234\u2013239 (2013).","journal-title":"Science China. Life sciences"},{"key":"BFsrep45932_CR35","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.humpath.2007.06.004","volume":"39","author":"HM Abdul-Al","year":"2008","unstructured":"Abdul-Al, H. M., Makhlouf, H. R., Wang, G. & Goodman, Z. D. Glypican-3 expression in benign liver tissue with active hepatitis C: implications for the diagnosis of hepatocellular carcinoma. Human pathology 39, 209\u2013212 (2008).","journal-title":"Human pathology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep45932.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep45932","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/srep45932","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/srep45932.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T23:36:39Z","timestamp":1671838599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep45932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,5]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,5,31]]}},"alternative-id":["BFsrep45932"],"URL":"https:\/\/doi.org\/10.1038\/srep45932","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,5]]},"assertion":[{"value":"19 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"45932"}}