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Proteomic profiling offers a promising approach to uncover specific biomarkers that could refine diagnostic accuracy, monitor disease activity, and guide therapeutic strategies. Our primary aim is to identify novel biomarkers for PSC-IBD and conventional ulcerative colitis (UC) via proteomic approach. The secondary aim is to advance the etiopathogenic understanding of the diseases by linking specific proteomic profiles with disease phenotypes. This single-center, prospective, biomarker-discovery study will involve 50 participants with PSC-IBD, 50 with UC, and 50 healthy controls. Biopsy samples from five bowel segments will be analyzed for proteomic signatures by an untargeted approach. The findings will subsequently undergo multi-step external validation in separate cohorts of 30 patients with PSC-IBD and 30 with UC, utilizing targeted proteomics, immunohistochemistry, and ELISA in bowel mucosa and peripheral blood, respectively. This proposed study aims to identify novel biomarkers to improve the diagnostic accuracy of PSC-IBD and UC and refine the disease activity assessment. Its robust design and large sample size provide a strong foundation for successful biomarker identification, with the potential to enhance clinical management of patients.<\/jats:p>","DOI":"10.1371\/journal.pone.0341885","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T18:31:51Z","timestamp":1769538711000},"page":"e0341885","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identifying biomarkers for diagnosis and disease activity monitoring in PSC-IBD and UC through proteomic profiling: A prospective, biomarker discovery single-center study protocol"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0393-2415","authenticated-orcid":true,"given":"Ondrej","family":"Fabian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Bajer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Macinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Brezina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojmir","family":"Hlavaty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Drastich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Wohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Harant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Talacko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sticova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8473-8664","authenticated-orcid":true,"given":"Andrea","family":"Vajsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0573-6684","authenticated-orcid":true,"given":"Alena","family":"Bohdanecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Tichanek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Cahova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"issue":"3","key":"pone.0341885.ref001","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.gtc.2014.05.003","article-title":"Immunology of inflammatory bowel disease and molecular targets for biologics","volume":"43","author":"M Dave","year":"2014","journal-title":"Gastroenterol Clin North Am"},{"issue":"1","key":"pone.0341885.ref002","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1152\/physrev.00003.2008","article-title":"Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer","volume":"91","author":"A Fasano","year":"2011","journal-title":"Physiol Rev"},{"issue":"12","key":"pone.0341885.ref003","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.3390\/nu13124259","article-title":"Gut Microbial Metabolite-Mediated Regulation of the Intestinal Barrier in the Pathogenesis of Inflammatory Bowel Disease","volume":"13","author":"N Iyer","year":"2021","journal-title":"Nutrients"},{"issue":"10","key":"pone.0341885.ref004","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1136\/gut.21.10.870","article-title":"Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology","volume":"21","author":"RW Chapman","year":"1980","journal-title":"Gut"},{"issue":"2","key":"pone.0341885.ref005","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/hep.23294","article-title":"Diagnosis and management of primary sclerosing cholangitis","volume":"51","author":"R Chapman","year":"2010","journal-title":"Hepatology"},{"issue":"1","key":"pone.0341885.ref006","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1067\/mge.2002.125367","article-title":"Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis","volume":"56","author":"RM Soetikno","year":"2002","journal-title":"Gastrointest Endosc"},{"issue":"4","key":"pone.0341885.ref007","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.crohns.2009.07.001","article-title":"Frequency of indeterminate colitis in children and adults with IBD - 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