{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:50:55Z","timestamp":1790221855735,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:p>Children with biliary atresia (BA) often develop portal hypertension (PHT) and its complications, which are associated with high morbidity and mortality. The goal of this study was to identify serum biomarkers of PHT by using large\u2010scale proteomics. We applied the slow off\u2010rate modified aptamer scan (SOMAscan) to measure 1,305 proteins in serum samples of children with BA with and without clinical evidence of PHT in validation and discovery cohorts enrolled in the Biliary Atresia Study of Infants and Children. Serum proteomics data was analyzed using logistic regression to identify protein(s) with an area under the receiver operating characteristic curve (AUROC)\u00a0\u2265\u00a00.90. Immunostaining was used to characterize the cellular localization of the new biomarker proteins in liver tissues. We identified nine proteins in the discovery cohort (n\u00a0=\u00a040 subjects) and five proteins in the validation cohort (n\u00a0=\u00a080 subjects) that individually or in combination predicted clinical PHT with AUROCs\u00a0\u2265\u00a00.90. Merging the two cohorts, we found that semaphorin 6B (SEMA6B) alone and three other protein combinations (SEMA6B+secreted frizzle protein 3 [SFRP3], SEMA6B+COMM domain containing 7 [COMMD7], and vascular cell adhesion molecule 1 [VCAM1]+BMX nonreceptor tyrosine kinase [BMX]) had AUROCs\u00a0\u2265\u00a00.90 in both cohorts, with high positive\u2010 and negative\u2010predictive values. Immunostaining of the new protein biomarkers showed increased expression in hepatic endothelial cells, cholangiocytes, and immune cells within portal triads in BA livers with clinical PHT compared to healthy livers. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Large\u2010scale proteomics identified SEMA6B, SFRP3, COMMD7, BMX, and VCAM1 as biomarkers highly associated with clinical PHT in BA. The expression of the biomarkers in hepatic epithelial, endothelial, and immune cells support their potential role in the pathophysiology of PHT.<\/jats:p>","DOI":"10.1002\/hep4.1878","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T06:47:00Z","timestamp":1640674020000},"page":"995-1004","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["Serum Proteomics Uncovers Biomarkers of Clinical Portal Hypertension in Children With Biliary Atresia"],"prefix":"10.1097","volume":"6","author":[{"given":"Julie","family":"Osborn","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Mourya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and 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Medicine,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranavkumar","family":"Shivakumar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH,USA"},{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9667-7742","authenticated-orcid":false,"given":"Jorge A.","family":"Bezerra","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH,USA"},{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"issue":"Suppl. 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