{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:17:57Z","timestamp":1787725077858,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Differentiating Crohn's disease (CD) from ulcerative colitis (UC) is challenging, often resulting as Inflammatory bowel disease unclassified (IBDU). Based on targeted RNA sequencing, we recently reported a 3\u2010gene signature algorithm that distinguished CD from UC. This study evaluated its ability to classify IBDU cases and explore disease biology. We analyzed 197 mucosal FFPE biopsies (inflamed and non\u2010inflamed) from 113 individuals at diagnosis: CD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200942), UC (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200941) and IBDU (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009102; follow\u2010up: 0\u201323\u2009years (IQR)). Expression levels of ANXA1, PI3, and VDR mRNAs were measured by RT\u2010qPCR, and assessed using logistic regression, and ROC curve analysis. The algorithm discriminated CD from UC with AUC values &gt;\u20090.70 in 6 out of 8 patient subsets, peaking in inflamed adult biopsies (0.78, 95% CI: 0.64\u20130.92). At 80% sensitivity, specificity ranged from 46% to 58%, replicating previous cohort findings and confirming reproducibility. Application of the algorithm to the IBDU cases showed low classification accuracy, with frequent misclassification of cases that were later received definitive diagnoses. Incorporation of additional IBDU\u2010specific features did not improve performance. While the 3\u2010gene signature algorithm demonstrates moderate ability to distinguish CD from UC, its limited performance in IBDU cases highlights fundamental constraints of binary classification approaches in IBD.\n                  <\/jats:p>","DOI":"10.1111\/apm.70245","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T02:20:56Z","timestamp":1786414856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Sub\u2010Classification Suggests\n                    <scp>IBD<\/scp>\n                    Unclassified as a Distinct Subtype of Inflammatory Bowel Disease: Insights From a 3\u2010Gene Mucosal Signature"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-7496","authenticated-orcid":false,"given":"Jaslin P.","family":"James","sequence":"first","affiliation":[{"name":"Department of Pathology Herlev University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ib Jarle","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Pathology Herlev University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-3567","authenticated-orcid":false,"given":"Boye S.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Bioneer A\/S  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8558-8442","authenticated-orcid":false,"given":"Ebbe","family":"Langholz","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Herlev University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-5658","authenticated-orcid":false,"given":"Estrid","family":"H\u00f8gdall","sequence":"additional","affiliation":[{"name":"Department of Pathology Herlev University Hospital  Herlev Denmark"},{"name":"Institute for Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene Buhl","family":"Riis","sequence":"additional","affiliation":[{"name":"Department of Pathology Herlev University Hospital  Herlev Denmark"},{"name":"Institute for Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CROHNS.2013.06.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/GUT.50.SUPPL_3.III37"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)32126\u20102"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)60026\u20109"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i1.21"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20361"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(21)00214\u20104"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.108043"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.058560"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izy046"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.149"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000811"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12865\u2010015\u20100069\u20100"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0297353"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21217893"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.02.083"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2011.647065"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12160"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201045569\u20103"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjx053"},{"key":"e_1_2_10_22_1","first-page":"400","article-title":"Ulcerative Colitis. An Epidemiological Study Based on a Regional Inception Cohort, With Special Reference to Disease Course and Prognosis","volume":"46","author":"Langholz E.","year":"1999","journal-title":"Danish Medical Bulletin"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/MPS7060101\/S1"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00185.2006"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/IBD\/IZAB311"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.21037\/TGH\u201024\u2010117\/COIF"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2024.05.033"}],"container-title":["APMIS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apm.70245","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apm.70245","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apm.70245","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:22:40Z","timestamp":1787721760000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apm.70245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/apm.70245"],"URL":"https:\/\/doi.org\/10.1111\/apm.70245","archive":["Portico"],"relation":{},"ISSN":["0903-4641","1600-0463"],"issn-type":[{"value":"0903-4641","type":"print"},{"value":"1600-0463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70245"}}