{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T01:03:15Z","timestamp":1784509395684,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Resolu\u00e7\u00e3o","award":["SES\/MG 7795"],"award-info":[{"award-number":["SES\/MG 7795"]}]},{"name":"State Funding Agency of Minas Gerais","award":["FAPEMIG\/APQ-02810-21"],"award-info":[{"award-number":["FAPEMIG\/APQ-02810-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Leprosy presents a broad clinical\u2013immunological spectrum, whose heterogeneity challenges early diagnosis and disease stratification. Metabolomic approaches have emerged as promising tools for identifying potential biomarkers associated with the disease\u2019s pathophysiology. This study aimed to investigate metabolic profiles associated with the different clinical forms of leprosy using untargeted metabolomics in formalin-fixed paraffin-embedded (FFPE) tissue samples. A retrospective cross-sectional study was conducted with 55 patients classified according to the Ridley\u2013Jopling spectrum. Metabolites were extracted from FFPE skin biopsies and analyzed by liquid chromatography\u2013mass spectrometry (LC-MS). From 908 metabolites initially detected, 27 were retained after frequency filtering. Six metabolites ultimately met the criteria of one-way analysis of variance (ANOVA, p &lt; 0.05) and fold-change (FC \u2265 2.0) for differential expression, while N-stearoyl tryptophan was identified as an additional candidate metabolite based on its contribution to multivariate group discrimination. These included 11-hydroperoxy-H4-neuroprostane, which showed a specific association with bacterial load, and the Gly-Pro-Lys tripeptide, which correlated with markers of infection progression. Metabolomics applied to FFPE samples proved feasible for discriminating the clinical spectrum of leprosy and annotating signatures associated with immune response. This approach represents an innovative strategy for exploratory biomarker discovery using archived histopathological samples in translational research.<\/jats:p>","DOI":"10.3390\/microorganisms14071567","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:47:32Z","timestamp":1784508452000},"page":"1567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mass Spectrometry-Based Metabolomics in Formalin-Fixed Paraffin-Embedded Skin Biopsies Identifies Potential Candidate Biomarkers for Leprosy Progression Across the Ridley\u2013Jopling Clinical Spectrum"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6522-4705","authenticated-orcid":false,"given":"Noriel Viana","family":"Pereira","sequence":"first","affiliation":[{"name":"Graduate Program in Health Sciences, School of Medicine, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1404-8876","authenticated-orcid":false,"given":"Bruno de Carvalho","family":"Dornelas","sequence":"additional","affiliation":[{"name":"Pathology Unit, Hospital das Cl\u00ednicas, Federal University of Uberl\u00e2ndia, Brazilian Hospital Services Company (HC-UFU\/HU Brasil), Uberl\u00e2ndia 38405-302, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willian Vargas Ten\u00f3rio da","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Surgery, Hospital das Cl\u00ednicas, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14048-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Paulo Sanches","family":"Zana","sequence":"additional","affiliation":[{"name":"School of Medicine, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmundo Nunes dos Santos","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Pathology Unit, Hospital das Cl\u00ednicas, Federal University of Minas Gerais, Brazilian Hospital Services Company (HC-UFMG\/HU Brasil), Belo Horizonte 30130-100, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8675-6455","authenticated-orcid":false,"given":"Felipe dos Anjos","family":"Rodrigues Campos","sequence":"additional","affiliation":[{"name":"School of Medicine, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deiriene Rodrigues de Oliveira","family":"Campos","sequence":"additional","affiliation":[{"name":"Pathology Unit, Hospital das Cl\u00ednicas, Federal University of Uberl\u00e2ndia, Brazilian Hospital Services Company (HC-UFU\/HU Brasil), Uberl\u00e2ndia 38405-302, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiara da Costa","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute of Exact, Natural Sciences and Education, Federal University of Tri\u00e2ngulo Mineiro, Uberaba 38064-200, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebreia Oliveira Almeida de","family":"Souza","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38405-320, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7381-2788","authenticated-orcid":false,"given":"M\u00e1rio Machado","family":"Martins","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38405-320, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1803-4861","authenticated-orcid":false,"given":"Luiz Ricardo","family":"Goulart Filho","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38405-320, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela Maria Bernardes","family":"Goulart","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, School of Medicine, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"},{"name":"School of Medicine, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"},{"name":"National Reference Center for Leprosy and Sanitary Dermatology (CREDESH), HC-UFU\/HU Brasil, Uberl\u00e2ndia 38405-302, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, X., Ma, Y., Li, G., Jin, G., Xu, L., Li, Y., Wei, P., and Zhang, L. 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