CDC6: A novel canine tumour biomarker detected in circulating extracellular vesicles

Vet Comp Oncol . 2021 Nov 7. doi: 10.1111/vco.12781. Online ahead of print. Anneloes Andriessen 1 2 , Laura Bongiovanni 1 3 , Tom A P Driedonks 1 , Elsbeth van Liere 1 , Anne Seijger 1 , Charlotte V Hegeman 1 , Sebastiaan A van Nimwegen 2 , Sara Galac 2 , Bart Westendorp 1 , Esther N M Nolte-T Hoen 1 , Alain de Bruin 1 3 Affiliations Expand Affiliations 1 Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. 2 Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. 3 Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Item in Clipboard Anneloes Andriessen et al. Vet Comp Oncol. 2021. Show details Display options Display options Format Vet Comp Oncol . 2021 Nov 7. doi: 10.1111/vco.12781. Online ahead of print. Authors Anneloes Andriessen 1 2 , Laura Bongiovanni 1 3 , Tom A P Driedonks 1 , Elsbeth van Liere 1 , Anne Seijger 1 , Charlotte V Hegeman 1 , Sebastiaan A van Nimwegen 2 , Sara Galac 2 , Bart Westendorp 1 , Esther N M Nolte-T Hoen 1 , Alain de Bruin 1 3 Affiliations 1 Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. 2 Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. 3 Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Item in Clipboard CiteDisplay options Display options Format Abstract Circulating nucleic acids and extracellular vesicles (EV) represent novel biomarkers to diagnose cancer. The non-invasive nature of these so-called liquid biopsies provides an attractive alternative to tissue biopsy-based cancer diagnostics. This study aimed to investigate if circulating cell cycle-related E2F target transcripts can be used to diagnose tumours in canine tumour patients with different types of tumours. Furthermore, we assessed if these mRNAs are localized within circulating EV. We isolated total RNA from the plasma of 20 canine tumour patients and 20 healthy controls. Four E2F target genes (CDC6, DHFR, H2AFZ and ATAD2) were selected based on the analysis of published data of tumour samples available in public databases. We performed RT-qPCR to analyse the plasma levels of selected E2F target transcripts. All four E2F target transcripts were detectable in the plasma of canine tumour patients. CDC6 mRNA levels were significantly higher in the plasma of canine tumour patients compared to healthy controls. A subset of canine tumour patient and healthy control plasma samples (n = 7) were subjected to size exclusion chromatography in order to validate association of the E2F target transcripts to circulating EV. For CDC6, EV analysis enhanced their detectability compared to total plasma analysis. In conclusion, our study reveals circulating CDC6 as a promising non-invasive biomarker to diagnose canine tumours. This article is protected by copyright. All rights reserved. Keywords: Biomarkers, Tumor; Cell Cycle; Dogs; Extracellular Vesicles; Liquid Biopsy. This article is protected by copyright. All rights reserved. [x] Cite Copy Format: Send To [x]