{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:10:30Z","timestamp":1789535430418,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Biliary atresia (BA) is a progressive obliteration of intrahepatic and extrahepatic bile ducts. Our study aimed to identify and validate hub genes that are differentially expressed in BA, and to investigate their relationship with liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The BA microarray datasets GSE46960 and GSE15235 were downloaded from the Gene Expression Omnibus (GEO) database. Clinical BA liver tissue samples were collected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB). Serum samples were analyzed for MFAP4 content using enzyme-linked immunosorbent assay (ELISA), and the corresponding clinical data of pediatric patients were collected. The relationship between serum MFAP4 levels and liver fibrosis, as well as prognosis, was investigated using ROC curve analysis. Furthermore, Kaplan\u2013Meier (KM) curves were used to validate the prognostic significance of MFAP4 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Through bioinformatics analysis and experimental validation, MFAP4 was identified as a hub gene. MFAP4 via PCR and immunohistochemistry is significantly upregulated in biliary atresia compared to total functional cyst liver tissue. Serum MFAP4 levels accurately reflects the degree of liver fibrosis in patients with BA. High serum MFAP4 levels predicted a poorer native liver survival rate one year after Kasai surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We discovered that MFAP4 is a crucial BA-associated gene, and validated its expression in BA. Furthermore, serum MFAP4 levels may serve as predictive markers for the degree of liver fibrosis and autologous liver survival after Kasai surgery.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1611564","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:10:46Z","timestamp":1748232646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["MFAP4 as a novel biomarker for predicting liver fibrosis and prognosis in infants with biliary atresia through the integration of bioinformatics with clinical data analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Chunxiao","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghua","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3389\/fimmu.2020.00329","article-title":"Innate immunity and pathogenesis of biliary atresia","volume":"11","author":"Ortiz-Perez","year":"2020","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1016\/S0140-6736(09)60946-6","article-title":"Biliary atresia","volume":"374","author":"Hartley","year":"2009","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1002\/hep.29905","article-title":"Biliary atresia: clinical and research challenges for the twenty-first century","volume":"68","author":"Bezerra","year":"2018","journal-title":"Hepatology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1007\/s00383-017-4172-6","article-title":"Update on investigations pertaining to the pathogenesis of biliary atresia","volume":"33","author":"Kilgore","year":"2017","journal-title":"Pediatr Surg Int"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/S0140-6736(17)32284-5","article-title":"Advances in paediatric gastroenterology","volume":"390","author":"Tam","year":"2017","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol Asp Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"875","DOI":"10.3390\/cells9040875","article-title":"Liver fibrosis: mechanistic concepts and therapeutic perspectives","volume":"9","author":"Roehlen","year":"2020","journal-title":"Cells"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.3390\/cells10102759","article-title":"Cellular and molecular mechanisms underlying liver fibrosis regression","volume":"10","author":"Caligiuri","year":"2021","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s12519-018-0203-1","article-title":"Liver fibrosis in biliary atresia","volume":"15","author":"Shen","year":"2019","journal-title":"World J Pediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1080\/17474124.2023.2191188","article-title":"Advances in understanding of biliary atresia pathogenesis and progression\u2014a riddle wrapped in a mystery inside an enigma","volume":"17","author":"Davenport","year":"2023","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1002\/hep.27045","article-title":"Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease","volume":"60","author":"Bessho","year":"2014","journal-title":"Hepatology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/gm154","article-title":"Staging of biliary atresia at diagnosis by molecular profiling of the liver","volume":"2","author":"Moyer","year":"2010","journal-title":"Genome Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"Clusterprofiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B14","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/nrgastro.2015.74","article-title":"Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes","volume":"12","author":"Asai","year":"2015","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2016.06.005","article-title":"Biliary atresia: a comprehensive review","volume":"73","author":"Lakshminarayanan","year":"2016","journal-title":"J Autoimmun"},{"key":"B16","doi-asserted-by":"crossref","first-page":"17437","DOI":"10.1016\/S0021-9258(18)71514-7","article-title":"Isolation and characterization of a new 36-kDa microfibril-associated glycoprotein from porcine aorta","volume":"264","author":"Kobayashi","year":"1989","journal-title":"J Biol Chem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1002\/hep.22764","article-title":"Detection of novel biomarkers of liver cirrhosis by proteomic analysis","volume":"49","author":"M\u00f6lleken","year":"2009","journal-title":"Hepatology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"764337","DOI":"10.3389\/fcvm.2021.764337","article-title":"MFAP4 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation through regulation of macrophage infiltration and activity","volume":"8","author":"Pilecki","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1002\/hep.31215","article-title":"Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury","volume":"72","author":"Terkelsen","year":"2020","journal-title":"Hepatology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","article-title":"Fibrosis: from mechanisms to medicines","volume":"587","author":"Henderson","year":"2020","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ceb.2018.08.004","article-title":"Signal transduction via integrin adhesion complexes","volume":"56","author":"Humphries","year":"2019","journal-title":"Curr Opin Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1111\/liv.14491","article-title":"Prediction of liver fibrosis severity in alcoholic liver disease by human microfibrillar-associated protein 4","volume":"40","author":"Madsen","year":"2020","journal-title":"Liver Int"},{"key":"B23","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1097\/HEP.0000000000000835","article-title":"Serum matrix metalloproteinase-7 (MMP-7): as good as it gets?","volume":"80","author":"Davenport","year":"2024","journal-title":"Hepatology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1002\/hep.32777","article-title":"Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease","volume":"77","author":"Leung","year":"2023","journal-title":"Hepatology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1097\/MPG.0000000000003792","article-title":"Matrix metalloproteinase-7 and osteopontin serum levels as biomarkers for biliary atresia","volume":"77","author":"Aldeiri","year":"2023","journal-title":"J Pediatr Gastroenterol Nutr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1611564\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:10:46Z","timestamp":1748232646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1611564\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":25,"alternative-id":["10.3389\/fped.2025.1611564"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1611564","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]},"article-number":"1611564"}}