{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:53:33Z","timestamp":1740142413349,"version":"3.37.3"},"reference-count":35,"publisher":"FapUNIFESP (SciELO)","issue":"3","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq. Gastroenterol."],"abstract":"<jats:p>ABSTRACT Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. Objective: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), \u03b2-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. Methods: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. Results: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of \u03b2-catenin, compared to stage-B patients (P&lt;0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). Conclusion The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.<\/jats:p>","DOI":"10.1590\/s0004-2803.202203000-71","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T19:44:52Z","timestamp":1662752692000},"page":"394-401","source":"Crossref","is-referenced-by-count":1,"title":["GENES EXPRESSION AND SERUM BIOMARKERS FOR DIAGNOSIS OF HEPATOCELLULAR CARCINOMA, CIRRHOSIS AND HEPATITIS C"],"prefix":"10.1590","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5250-6212","authenticated-orcid":false,"given":"Rafael","family":"FERNANDES-FERREIRA","sequence":"first","affiliation":[{"name":"Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio Preto, Brasil; Universidade Paulista, Brasil; Universidade de Campinas, Brasil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3341-9193","authenticated-orcid":false,"given":"Graciele Domitila","family":"TENANI","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio Preto, Brasil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3645-3709","authenticated-orcid":false,"given":"Marcela Augusta de Souza","family":"PINHEL","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo, Brasil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-7871","authenticated-orcid":false,"given":"Ana Margarida Coelho","family":"ABRANTES","sequence":"additional","affiliation":[{"name":"University of Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-1650","authenticated-orcid":false,"given":"Maria Filomena Raba\u00e7a Roque","family":"BOTELHO","sequence":"additional","affiliation":[{"name":"University of Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6302-0939","authenticated-orcid":false,"given":"Rita de C\u00e1ssia Martins Alves da","family":"SILVA","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio Preto, Brasil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-2325","authenticated-orcid":false,"given":"Dorot\u00e9ia Rossi Silva","family":"SOUZA","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio Preto, Brasil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-6426","authenticated-orcid":false,"given":"Renato Ferreira da","family":"SILVA","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio Preto, Brasil"}]}],"member":"530","published-online":{"date-parts":[[2022,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijsu.2020.04.043","article-title":"Emerging biomarkers in HCC patients: Current status","volume":"82","author":"Marques HP","year":"2020","journal-title":"Int J Surg"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s15010-019-01345-y","article-title":"Epidemiological and etiological variations in hepatocellular carcinoma","volume":"48","author":"Sagnelli E","year":"2020","journal-title":"Infection"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"7316","DOI":"10.3748\/wjg.v19.i42.7316","article-title":"Multimodal treatment of hepatocellular carcinoma on cirrhosis: An update","volume":"19","author":"Vivarelli M","year":"2013","journal-title":"World J Gastroenterol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.3892\/ijo.2013.1829","article-title":"Human hepatocyte carcinogenesis","volume":"42","author":"Shiraha H","year":"2013","journal-title":"Int J Oncol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"130","DOI":"10.2174\/138920211795564359","article-title":"Genetic and Epigenetic Signatures in Human Hepatocellular Carcinoma: A Systematic Review","volume":"12","author":"Nishida N","year":"2011","journal-title":"Curr Genomics"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1055\/s-2007-1007122","article-title":"Prognosis of Hepatocellular Carcinoma: The BCLC Staging Classification","volume":"19","author":"Llovet J","year":"1999","journal-title":"Semin Liver Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen TD","year":"2008","journal-title":"Nat Protoc"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"17453","DOI":"10.4238\/2015.December.21.16","article-title":"Influence of vascular endothelial growth factor and alpha-fetoprotein on hepatocellular carcinoma","volume":"14","author":"Yvamoto EY","year":"2015","journal-title":"Genet Mol Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1111\/j.1349-7006.2008.00909.x","article-title":"Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients","volume":"99","author":"Shim JH","year":"2008","journal-title":"Cancer Sci"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ajg.2016.06.005","article-title":"The role of vascular endothelial growth factor \u2212634 G\/C and its soluble receptor on chronic liver disease and hepatocellular carcinoma","volume":"17","author":"Ratnasari N","year":"2016","journal-title":"Arab J Gastroenterol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara N","year":"2003","journal-title":"Nat Med"},{"key":"ref12","first-page":"209","article-title":"Serum VEGF level is associated with the outcome of patients with hepatocellular carcinoma: a meta-analysis","volume":"2","author":"Zhan P","year":"2013","journal-title":"Hepatobiliary Surg Nutr"},{"key":"ref13","doi-asserted-by":"crossref","DOI":"10.1016\/j.urology.2012.01.016","article-title":"Vascular Endothelial Growth Factor, Carbonic Anhydrase 9, and Angiogenin as Urinary Biomarkers for Bladder Cancer Detection","volume":"79","author":"Urquidi V","year":"2012","journal-title":"Urology"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/ijc.28109","article-title":"Polymorphisms in the VEGFA promoter are associated with susceptibility to hepatocellular carcinoma by altering promoter activity","volume":"133","author":"Wu X","year":"2013","journal-title":"Int J Cancer"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"9607054","DOI":"10.1155\/2016\/9607054","article-title":"VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma","volume":"2016","author":"Baitello ME","year":"2016","journal-title":"Can J Gastroenterol Hepatol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.3748\/wjg.v16.i28.3521","article-title":"Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma","volume":"16","author":"Akutsu N","year":"2010","journal-title":"World J Gastroenterol"},{"key":"ref17","first-page":"2021","article-title":"Gene Expression Analysis for Evaluation of Potential Biomarkers in Hepatocellular Carcinoma","volume":"35","author":"Hass H","year":"2015","journal-title":"Anticancer Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.3748\/wjg.v18.i19.2408","article-title":"Glypican-3 expression and its relationship with recurrence of HCC after liver transplantation","volume":"18","author":"Wang Y-L","year":"2012","journal-title":"World J Gastroenterol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00535-013-0793-2","article-title":"Positive glypican-3 expression in early hepatocellular carcinoma predicts recurrence after hepatectomy","volume":"49","author":"Chen I-P","year":"2013","journal-title":"J Gastroenterol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/127831","article-title":"Can Serum Glypican-3 Be a Biomarker for Effective Diagnosis of Hepatocellular Carcinoma? A Meta-Analysis of the Literature","volume":"2014","author":"Yang S-L","year":"2014","journal-title":"Dis Markers"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3748\/wjg.v22.i1.275","article-title":"Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma","volume":"22","author":"Haruyama Y","year":"2016","journal-title":"World J Gastroenterol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.5009\/gnl.2014.8.2.177","article-title":"Clinical Utility of Plasma Glypican-3 and Osteopontin as Biomarkers of Hepatocellular Carcinoma","volume":"8","author":"Lee HJ","year":"2014","journal-title":"Gut Liver"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.3748\/wjg.v21.i18.5654","article-title":"Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging","volume":"21","author":"Gomaa AI","year":"2015","journal-title":"World J Gastroenterol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/hep.25950","article-title":"Performance status in patients with hepatocellular carcinoma: Determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system","volume":"57","author":"Hsu C-Y","year":"2013","journal-title":"Hepatology"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/13651820410024049","article-title":"Diagnosis of hepatocellular carcinoma","volume":"7","author":"Bialecki ES","year":"2005","journal-title":"HPB"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1158\/1078-0432.CCR-07-1615","article-title":"Identification of Cystatin B as a Potential Serum Marker in Hepatocellular Carcinoma","volume":"14","author":"Lee M-J","year":"2008","journal-title":"Clin Cancer Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1590\/S1516-89132003000100014","article-title":"Cysteine proteinases and cystatins","volume":"46","author":"Oliveira AS","year":"2003","journal-title":"Brazilian Archives of Biology and Technology"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"21215","DOI":"10.3402\/ijch.v72i0.21215","article-title":"Evaluation of serum procathepsin B, cystatin B and cystatin C as possible biomarkers of ovarian cancer","volume":"72","author":"Gashenko EA","year":"2013","journal-title":"Int J Circumpolar Health"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.3892\/ijo.2015.2858","article-title":"Cystatin B as a potential diagnostic biomarker in ovarian clear cell carcinoma","volume":"46","author":"Takaya A","year":"2015","journal-title":"Int J Oncol"},{"key":"ref30","first-page":"3190","article-title":"Expression of Wnt-5a and \u03b2-catenin in primary hepatocellular carcinoma","volume":"7","author":"Li P","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1600-0463.2012.02947.x","article-title":"The expression and significance of WWOX and \u03b2-catenin in hepatocellular carcinoma","volume":"121","author":"Li Y-P","year":"2012","journal-title":"APMIS"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.tcb.2003.11.004","article-title":"The ins and outs of Wingless signaling","volume":"14","author":"Seto ES","year":"2004","journal-title":"Trends Cell Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"708","DOI":"10.3389\/fonc.2019.00708","article-title":"The Role of Glypican-3 in Regulating Wnt, YAP, and Hedgehog in Liver Cancer","volume":"9","author":"Kolluri A","year":"2019","journal-title":"Front Oncol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.12659\/MSM.894669","article-title":"Comparative Metabolomic Profiling of Hepatocellular Carcinoma Cells Treated with Sorafenib Monotherapy vs Sorafenib-Everolimus Combination Therapy","volume":"21","author":"Zheng J-F","year":"2015","journal-title":"Med Sci Monit"},{"key":"ref35","first-page":"2054","article-title":"Bioinformatics analysis of gene expression. profiles in hepatocellular carcinoma","volume":"19","author":"Shangguan H","year":"2015","journal-title":"Eur Rev Med Pharmacol Sci"}],"container-title":["Arquivos de Gastroenterologia"],"original-title":["Express\u00e3o g\u00eanica e biomarcadores s\u00e9ricos para diagn\u00f3stico de carcinoma hepatocelular, cirrose e hepatite C"],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S0004-28032022000300394&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,26]],"date-time":"2023-11-26T20:00:49Z","timestamp":1701028849000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0004-28032022000300394&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["S0004-28032022000300394"],"URL":"https:\/\/doi.org\/10.1590\/s0004-2803.202203000-71","relation":{},"ISSN":["1678-4219","0004-2803"],"issn-type":[{"type":"electronic","value":"1678-4219"},{"type":"print","value":"0004-2803"}],"subject":[],"published":{"date-parts":[[2022,9]]}}}