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

The identification of practical early diagnosis biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumour 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 tumour lesions. To enable earlier diagnosis, which is essential for the implementation of effective conservation strategies, we analysed the extracellular vesicle (EV) proteome of 87 Tasmanian devil serum samples. The antimicrobial peptide cathelicidin-3 (CATH3) was enriched in serum EVs 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). As antimicrobial peptides can play a variety of roles in the cancer process, our results suggest that the specific elevation of serum EV-associated CATH3 may be mechanistically involved in DFTD pathogenesis. 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 imperilled Tasmanian devil population.