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Cathelicidin-3 associated with serum extracellular vesicles enables early diagnosis of a transmissible cancer

Citation

Espejo, C and Wilson, R and Pye, RJ and Ratcliffe, JC and Ruiz-Aravena, M and Willms, E and Wolfe, BW and Hamede, R and Hill, AF and Jones, ME and Woods, GM and Lyons, AB, Cathelicidin-3 associated with serum extracellular vesicles enables early diagnosis of a transmissible cancer, Frontiers in Immunology, 13 pp. 1-14. ISSN 1664-3224 (2022) [Refereed Article]


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DOI: doi:10.3389/fimmu.2022.858423

Abstract

The identification of practical early diagnostic biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumor disease (DFTD), a highly lethal transmissible cancer afflicting virtually an entire species, the Tasmanian devil (Sarcophilus harrisii). Despite a latent period that can exceed one year, to date DFTD diagnosis requires visual identification of tumor lesions. To enable earlier diagnosis, which is essential for the implementation of effective conservation strategies, we analyzed the extracellular vesicle (EV) proteome of 87 Tasmanian devil serum samples using data-independent acquisition mass spectrometry approaches. The antimicrobial peptide cathelicidin-3 (CATH3), released by innate immune cells, was enriched in serum EV samples of both devils with clinical DFTD (87.9% sensitivity and 94.1% specificity) and devils with latent infection (i.e., collected while overtly healthy, but 3-6 months before subsequent DFTD diagnosis; 93.8% sensitivity and 94.1% specificity). Although high expression of antimicrobial peptides has been mostly related to inflammatory diseases, our results suggest that they can be also used as accurate cancer biomarkers, suggesting a mechanistic role in tumorous processes. This EV-based approach to biomarker discovery is directly applicable to improving understanding and diagnosis of a broad range of diseases in other species, and these findings directly enhance the capacity of conservation strategies to ensure the viability of the imperiled Tasmanian devil population.

Item Details

Item Type:Refereed Article
Keywords:exosomes, microvesicles, innate immunity, liquid biopsy, animal models, early cancer detection, proteomics, cathelicidins
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Tumour immunology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Espejo, C (Mrs Camila Espejo)
UTAS Author:Wilson, R (Dr Richard Wilson)
UTAS Author:Pye, RJ (Ms Ruth Pye)
UTAS Author:Ruiz-Aravena, M (Mr Manuel Ruiz Aravena)
UTAS Author:Wolfe, BW (Mr Barrett Wolfe)
UTAS Author:Hamede, R (Dr Rodrigo Hamede Ross)
UTAS Author:Jones, ME (Mr Jones)
UTAS Author:Woods, GM (Professor Gregory Woods)
UTAS Author:Lyons, AB (Associate Professor Bruce Lyons)
ID Code:154957
Year Published:2022
Deposited By:Menzies Institute for Medical Research
Deposited On:2023-01-20
Last Modified:2023-01-20
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