Peptidomics Unveils Distinct Acetylation Patterns of Histone and Annexin A1 in Differentiated Thyroid Cancer

Author:

Coelho Margarida1234ORCID,Capela João5ORCID,Mendes Vera M.123,Pacheco João5ORCID,Fernandes Margarida Sá5,Amendoeira Isabel567,Jones John G.123ORCID,Raposo Luís89ORCID,Manadas Bruno123ORCID

Affiliation:

1. CNC—Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal

2. CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal

3. III Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal

4. Department of Chemistry, Faculty of Sciences and Technology, University of Coimbra, 3004-535 Coimbra, Portugal

5. Centro Hospitalar Universitário São João, 4200-319 Porto, Portugal

6. I3S, Instituto de Investigação e Inovação em Saúde, 4200-135 Porto, Portugal

7. Ipatimup, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-465 Porto, Portugal

8. Portuguese Society of Endocrinology, Diabetes and Metabolism, 1600-892 Lisbon, Portugal

9. EPIUnit, Institute of Public Health, University of Porto, 4050-600 Porto, Portugal

Abstract

Thyroid cancer is a common malignancy of the endocrine system. 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.

Funder

Fundação para a Ciência e Tecnologia

European Regional Development Fund

Centro 2020 Regional Operational Programme

COMPETE 2020—Operational Programme for Competitiveness and Internationalisation

Portuguese national funds

National Mass Spectrometry Network

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference38 articles.

1. Malignancy rates in thyroid nodules: A long-term cohort study of 17,592 patients;Grussendorf;Eur. Thyroid. J.,2022

2. Molecular genetics and diagnosis of thyroid cancer;Nikiforov;Nat. Rev. Endocrinol.,2011

3. The 2023 Bethesda System for Reporting Thyroid Cytopathology;Ali;Thyroid,2023

4. Thyroid tumors: Novel insights from proteomic studies;Damante;Expert Rev. Proteom.,2009

5. Proteome analysis in thyroid pathology;Pagni;Expert Rev. Proteom.,2015

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