{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T02:34:59Z","timestamp":1770518099512,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIRCS-Italian Association for Sclerosing Cholangitis Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers. Methods: Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography\u2013tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group. Results: We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway. Conclusion: We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC.<\/jats:p>","DOI":"10.3390\/jcm13020544","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T06:41:22Z","timestamp":1705560082000},"page":"544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Clinical Utility of the Saliva Proteome in Rare Diseases: A Pilot Study for Biomarker Discovery in Primary Sclerosing Cholangitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3912-2753","authenticated-orcid":false,"given":"Elisa","family":"Ceccherini","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1619-401X","authenticated-orcid":false,"given":"Elena","family":"Michelucci","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"},{"name":"Institute of Chemistry of Organometallic Compounds, National Research Council, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0067-2240","authenticated-orcid":false,"given":"Giovanni","family":"Signore","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"},{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9289-8131","authenticated-orcid":false,"given":"Barbara","family":"Coco","sequence":"additional","affiliation":[{"name":"Hepatology Unit, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Zari","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Bellini","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8364-9152","authenticated-orcid":false,"given":"Maurizia Rossana","family":"Brunetto","sequence":"additional","affiliation":[{"name":"Hepatology Unit, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Cecchettini","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3831-4200","authenticated-orcid":false,"given":"Silvia","family":"Rocchiccioli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.jhep.2017.07.022","article-title":"Primary Sclerosing Cholangitis\u2014A Comprehensive Review","volume":"67","author":"Karlsen","year":"2017","journal-title":"J. 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