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Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.<\/jats:p>","DOI":"10.3390\/ijms25010376","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T07:45:32Z","timestamp":1703663132000},"page":"376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Peptidomics Unveils Distinct Acetylation Patterns of Histone and Annexin A1 in Differentiated Thyroid Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-1118","authenticated-orcid":false,"given":"Margarida","family":"Coelho","sequence":"first","affiliation":[{"name":"CNC\u2014Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"III Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"Department of Chemistry, Faculty of Sciences and Technology, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5874-9677","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Capela","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Vera M.","family":"Mendes","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"III Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-9557","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Margarida S\u00e1","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Isabel","family":"Amendoeira","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"I3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"Ipatimup, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-3885","authenticated-orcid":false,"given":"John G.","family":"Jones","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"III Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1001-6017","authenticated-orcid":false,"given":"Lu\u00eds","family":"Raposo","sequence":"additional","affiliation":[{"name":"Portuguese Society of Endocrinology, Diabetes and Metabolism, 1600-892 Lisbon, Portugal"},{"name":"EPIUnit, Institute of Public Health, University of Porto, 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-4042","authenticated-orcid":false,"given":"Bruno","family":"Manadas","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"III Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e220027","DOI":"10.1530\/ETJ-22-0027","article-title":"Malignancy rates in thyroid nodules: A long-term cohort study of 17,592 patients","volume":"11","author":"Grussendorf","year":"2022","journal-title":"Eur. 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