{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:35:07Z","timestamp":1792859707571,"version":"4.5.0"},"reference-count":65,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472762"],"award-info":[{"award-number":["82472762"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Liver fibrosis and cirrhosis represent critical stages in the progression of chronic liver disease, yet their key molecular features remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental design<\/jats:title>\n                    <jats:p>We performed large\u2010scale Olink\u2010based proteomic profiling in over 40,000 participants from the UK Biobank with a median follow\u2010up of 15.6 years to elucidate disease pathophysiology and identify pre\u2010diagnostic biomarkers. Cross\u2010sectional analysis included 66 prevalent cirrhosis cases, and prospective analysis identified 224 incident cirrhosis cases. Machine learning and Mendelian randomization (MR) were applied. An independent cohort was used for validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Distinct dysregulated proteins were observed in compensated cirrhosis (CC) and decompensated cirrhosis (DC). In the prospective analysis, 696 proteins were associated with disease onset. A proteomic panel based on these markers achieved an AUC of 0.832 for predicting incident cirrhosis, outperforming established fibrosis scores including FIB\u20104, APRI, and NFS, and demonstrated robust performance across CC and DC populations. The protein panel showed predictive value (AUC\u00a0=\u00a00.743) for disease progression in an independent cohort. MR identified 66 proteins with putative causal roles, including 11 potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and clinical relevance<\/jats:title>\n                    <jats:p>These findings provide novel molecular insights into cirrhosis development and support integrated proteomic biomarkers as a discovery and prioritization framework for early risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/prca.70050","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:59:16Z","timestamp":1786618756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Pre\u2010Diagnostic Protein Biomarkers for Liver Cirrhosis Based on Prospective Analysis of a Large\u2010Scale Plasma Proteomics in the UK Biobank"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8425-3481","authenticated-orcid":false,"given":"Jitian","family":"He","sequence":"first","affiliation":[{"name":"Organ Transplant Center The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Digestive System Department The Affiliated Guangdong Second Provincial General Hospital of Jinan University  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Yan","sequence":"additional","affiliation":[{"name":"Organ Transplant Center The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Organ Transplant Center The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of General Surgery Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of General Surgery Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6553-4458","authenticated-orcid":false,"given":"Chuanzhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou P. R. 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