{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:03:12Z","timestamp":1792184592786,"version":"4.4.0"},"reference-count":54,"publisher":"Korean Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-NR069128"],"award-info":[{"award-number":["RS-2022-NR069128"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00454407"],"award-info":[{"award-number":["RS-2024-00454407"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005006","name":"Asan Institute for Life Sciences, Asan Medical Center","doi-asserted-by":"publisher","award":["2024IP0054"],"award-info":[{"award-number":["2024IP0054"]}],"id":[{"id":"10.13039\/501100005006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-enm.org"],"crossmark-restriction":true},"short-container-title":["Endocrinol Metab"],"published-print":{"date-parts":[[2025,8,31]]},"abstract":"<jats:p>Background: The preoperative diagnosis of follicular thyroid carcinoma (FTC) is challenging because it cannot be readily distinguished from follicular adenoma (FA) or benign follicular nodular disease (FND) using the sonographic and cytological features typically employed in clinical practice.Methods: We employed comprehensive proteomics and machine learning (ML) models to identify novel diagnostic biomarkers capable of classifying three subtypes: FTC, FA, and FND. Bottom-up proteomics techniques were applied to quantify proteins in formalin-fixed, paraffin-embedded (FFPE) thyroid tissues. In total, 202 FFPE tissue samples, comprising 62 FNDs, 72 FAs, and 68 FTCs, were analyzed.Results: Close spectrum-spectrum matching quantified 6,332 proteins, with approximately 9% (780 proteins) differentially expressed among the groups. When applying an ML model to the proteomics data from samples with preoperative indeterminate cytopathology (n=183), we identified distinct protein panels: five proteins (CNDP2, DNAAF5, DYNC1H1, FARSB, and PDCD4) for the FND prediction model, six proteins (DNAAF5, FAM149B1, RPS9, TAGLN2, UPF1, and UQCRC1) for the FA model, and seven proteins (ACTN4, DSTN, MACROH2A1, NUCB1, SPTAN1, TAGLN, and XRCC5) for the FTC model. The classifiers\u2019 performance, evaluated by the median area under the curve values of the random forest models, was 0.832 (95% confidence interval [CI], 0.824 to 0.839) for FND, 0.826 (95% CI, 0.817 to 0.835) for FA, and 0.870 (95% CI, 0.863 to 0.877) for FTC.Conclusion: Quantitative proteome analysis combined with an ML model yielded an optimized multi\u2010protein panel that can distinguish FTC from benign subtypes. Our findings indicate that a proteomic approach holds promise for the differential diagnosis of FTC.<\/jats:p>","DOI":"10.3803\/enm.2024.2208","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T02:39:36Z","timestamp":1744252776000},"page":"623-636","update-policy":"https:\/\/doi.org\/10.3803\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comprehensive Proteomics and Machine Learning Analysis to Distinguish Follicular Adenoma and Follicular Thyroid Carcinoma from Indeterminate Thyroid Nodules"],"prefix":"10.3803","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2241-6536","authenticated-orcid":true,"given":"Hee-Sung","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae A","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Ji","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Mi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea-Yon","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Eun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyoung","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Min","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Sook","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-5331","authenticated-orcid":true,"given":"Kyunggon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8404-7759","authenticated-orcid":true,"given":"Won Gu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2119","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2012.0356"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0405"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.5858\/2008-132-622-ttgrpi"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2023.0141"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0247"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-010-0720-0"},{"key":"ref7","first-page":"1792","volume-title":"Classification of follicular thyroid tumors by molecular signature: results of gene profiling","author":"Barden","year":"2003"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1172\/jci200419617"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-07-5020"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-05-2226"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2017.07.003"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2022.0124"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab304"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002\/dc.24564"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2292"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-022-00442-x"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113844"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.02.039"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1002\/prca.200600381"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1530\/eje-11-0856"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrp.2022.101069"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1007\/s11831-020-09405-5"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1159\/000330778"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4256"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00359"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.45"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_7"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2435-4"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00291"},{"key":"ref30","first-page":"1260419","volume-title":"Proteomics: tissue-based map of the human proteome","author":"Uhlen","year":"2015"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.m800518-mcp200"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1021\/pr800503u"},{"key":"ref33","first-page":"417","volume-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","author":"Liberzon","year":"2015"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"ref35","first-page":"343","volume-title":"Strategies for dealing with missing data in clinical trials: from design to analysis","author":"Dziura","year":"2013"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1159\/000095850"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0184-8"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1113"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jasms.2008.12.014"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1309\/ajcpphlwmi3jv4la"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2017.0500"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0779"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000081"},{"key":"ref44","first-page":"23660","volume-title":"Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy","author":"Martinez-Aguilar","year":"2016"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.854611"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3191.309"},{"key":"ref47","first-page":"1551","volume-title":"FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models","author":"Mochizuki","year":"2001"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00082"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.13.11673"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-017-0661-0"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2006.07.014"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1991.tb00808.x"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj1954.37.247"},{"key":"ref54","first-page":"366","volume-title":"Differential oncogenic expression in thyroid follicular and Hurthle cell carcinomas","author":"Masood","year":"1993"}],"container-title":["Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-enm.org\/upload\/pdf\/enm-2024-2208.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-enm.org\/journal\/view.php?doi=10.3803\/EnM.2024.2208","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-enm.org\/upload\/pdf\/enm-2024-2208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T07:06:39Z","timestamp":1756710399000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-enm.org\/journal\/view.php?doi=10.3803\/EnM.2024.2208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,31]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"URL":"https:\/\/doi.org\/10.3803\/enm.2024.2208","relation":{},"ISSN":["2093-596X","2093-5978"],"issn-type":[{"value":"2093-596X","type":"print"},{"value":"2093-5978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,31]]},"assertion":[{"value":"2024-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-31","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}