Evaluation of Plasma Nucleosome Concentrations in Healthy Dogs and Dogs with Various Common Cancers

Abstract: Background

Nucleosomes are released into circulation during apoptosis or necrosis in a variety of diseases. Changes in plasma nucleosome concentrations have been reported to be useful epigenetic biomarkers for monitoring treatment response of a variety of cancers in humans. In dogs, elevated plasma nucleosome concentrations have been documented in lymphoma and hemangiosarcoma.



Hypothesis/Objectives

The objective of this study was to quantify and better characterize plasma nucleosomes in dogs with various common malignancies.



Animals

A total of 662 cancer patients and healthy dogs were included in this study (528 dogs with cancer and 134 healthy dogs).



Methods

Canine plasma samples from the NCI-DCTD biorepository and from active patients or healthy volunteers at a Small Animal Teaching Hospital were purchased or collected with owner consent and IACUC approval, respectively, for this study. Samples were processed immediately and then stored at -80C until they could be run in batches. The Nu.Q® H3.1 total nucleosome ELISA assay was performed according to the manufacturer’s protocol.



Results

The most common cancers evaluated included lymphoma (LSA; n=126), Hemangiosarcoma (HSA; n=77), osteosarcoma (OSA; n=49), soft tissue sarcoma (STS; 51), malignant melanoma (n=49), mast cell tumors (MCT; n=126) and histiocytic sarcoma (n=26). A receiver operator characteristic curve AUC was 68.7% for all cancers. Cancers with the highest AUCs included hemangiosarcoma (91.74%), lymphoma (87.83%), histiocytic sarcoma (83.01%) and malignant melanoma (75.05%).



Conclusion and Clinical Importance

This assay is useful for detecting common cancers that are more systemic or those that have a high cellular turnover rate.