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Cathelicidin-3 Associated With Serum Extracellular Vesicles Enables Early Diagnosis of a Transmissible Cancer

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posted on 04.05.2022, 07:16 authored by Camila Espejo, Richard Wilson, Ruth J Pye, Julian RatcliffeJulian Ratcliffe, Manuel Ruiz-Aravena, Eduard WillmsEduard Willms, Barrett W Wolfe, Rodrigo Hamede, Andrew HillAndrew Hill, Menna E Jones, Gregory M Woods, A Bruce Lyons
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.

History

Publication Date

01/01/2022

Journal

Frontiers in Immunology

Volume

13

Article Number

858423

Pagination

14p.

Publisher

Frontiers Media S.A.

ISSN

1664-3224

Rights Statement

© 2022 Espejo, Wilson, Pye, Ratcliffe, Ruiz-Aravena, Willms, Wolfe, Hamede, Hill, Jones, Woods and Lyons. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.