DAMPs and NETs in Thyroid Diseases: Biological, Diagnostic, and Translational Perspectives
- 11st Department of General and Endocrine Surgery, Medical University of Bialystok, 24a M. Sklodowskiej-Curie Street, 15-276 Bialystok, Poland
- 2Department of Hygiene, Epidemiology and Environmental Health, Medical University of Bialystok 2c A. Mickiewicza, 15-369 Bialystok, Poland
- 3Department of Minimally Invasive Surgery, Medical University of Bialystok, 24a M. Sklodowskiej-Curie Street, 15-276 Bialystok, Poland
Abstract
Thyroid diseases encompass a broad spectrum of autoimmune, inflammatory, and neoplastic disorders, yet current diagnostic approaches provide limited insight into innate immune activation and tumor-associated inflammatory remodeling. Damage-associated molecular patterns (DAMPs) and neutrophil extracellular traps (NETs) have emerged as interconnected mediators of sterile inflammation with potential relevance to thyroid carcinogenesis, disease progression, and biomarker development. This narrative review synthesized literature identified through PubMed/MEDLINE and Scopus to evaluate the biological, diagnostic, and translational significance of DAMP- and NET-associated pathways in thyroid diseases, with particular emphasis on thyroid cancer. DAMPs such as high-mobility group box 1 (HMGB1), S100A8/A9, serum amyloid A, heat shock proteins, and extracellular nucleic acids may sustain inflammatory signaling through pattern-recognition receptors and contribute to tumor proliferation, angiogenesis, immune modulation, and therapeutic resistance. In parallel, circulating analytes associated with NET biology—including nonspecific cell-free DNA (cfDNA) and nucleosomes, pathway-associated citrullinated histone H3 (CitH3), and composite myeloperoxidase–DNA (MPO–DNA) complexes—have shown associations with thyroid malignancy, dedifferentiated disease, metastatic presentation, and greater disease severity. Experimental data further suggest that aggressive thyroid cancer cells, particularly anaplastic thyroid carcinoma, can induce extracellular trap formation and exploit neutrophil-derived signals to support tumor growth. However, limited disease specificity, assay heterogeneity, and the predominance of small or exploratory cohorts currently restrict clinical implementation. Future strategies should prioritize standardized, prospective validation of multimarker panels integrating DAMP- and NET-related analytes with imaging, cytology, molecular diagnostics, and clinicopathological risk stratification to determine whether they provide incremental value for diagnosis, prognostication, and longitudinal monitoring in thyroid cancer.
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BibTeX
@article{waczynski2026damps,
title = {{DAMPs and NETs in Thyroid Diseases: Biological, Diagnostic, and Translational Perspectives}},
author = {Kamil Waczyński and Barbara Choromańska and Mateusz Maciejczyk and Marta Lewoc-Magnuszewska and Alan Tkaczuk and Julia Grymuza and Jacek Dadan and Piotr Myśliwiec},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213469},
url = {https://www.mdpi.com/2072-6694/18/21/3469},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DAMPs and NETs in Thyroid Diseases: Biological, Diagnostic, and Translational Perspectives
AU - Kamil Waczyński
AU - Barbara Choromańska
AU - Mateusz Maciejczyk
AU - Marta Lewoc-Magnuszewska
AU - Alan Tkaczuk
AU - Julia Grymuza
AU - Jacek Dadan
AU - Piotr Myśliwiec
PY - 2026
DA - 2026/10/27
JO - Cancers
DO - 10.3390/cancers18213469
UR - https://www.mdpi.com/2072-6694/18/21/3469
AB - Thyroid diseases encompass a broad spectrum of autoimmune, inflammatory, and neoplastic disorders, yet current diagnostic approaches provide limited insight into innate immune activation and tumor-associated inflammatory remodeling. Damage-associated molecular patterns (DAMPs) and neutrophil extracellular traps (NETs) have emerged as interconnected mediators of sterile inflammation with potential relevance to thyroid carcinogenesis, disease progression, and biomarker development. This narrative review synthesized literature identified through PubMed/MEDLINE and Scopus to evaluate the biological, diagnostic, and translational significance of DAMP- and NET-associated pathways in thyroid diseases, with particular emphasis on thyroid cancer. DAMPs such as high-mobility group box 1 (HMGB1), S100A8/A9, serum amyloid A, heat shock proteins, and extracellular nucleic acids may sustain inflammatory signaling through pattern-recognition receptors and contribute to tumor proliferation, angiogenesis, immune modulation, and therapeutic resistance. In parallel, circulating analytes associated with NET biology—including nonspecific cell-free DNA (cfDNA) and nucleosomes, pathway-associated citrullinated histone H3 (CitH3), and composite myeloperoxidase–DNA (MPO–DNA) complexes—have shown associations with thyroid malignancy, dedifferentiated disease, metastatic presentation, and greater disease severity. Experimental data further suggest that aggressive thyroid cancer cells, particularly anaplastic thyroid carcinoma, can induce extracellular trap formation and exploit neutrophil-derived signals to support tumor growth. However, limited disease specificity, assay heterogeneity, and the predominance of small or exploratory cohorts currently restrict clinical implementation. Future strategies should prioritize standardized, prospective validation of multimarker panels integrating DAMP- and NET-related analytes with imaging, cytology, molecular diagnostics, and clinicopathological risk stratification to determine whether they provide incremental value for diagnosis, prognostication, and longitudinal monitoring in thyroid cancer.
SN - 2072-6694
ER -