Relationship Between Plasma Cell-Free DNA Changes and Lysyl Oxidase During the Treatment and Prognosis of Canine Transmissible Venereal Tumor

Background: Transmissible Venereal Tumor (TVT) is a wide tumor of canine, there are no effective markers to monitor the therapeutic response in real-time. Circulating biomarkers may be valuable for the early diagnosis and prognosis of cancers, so in this study, we aimed to investigate the significance of the cell-free DNA (cfDNA) and cfDNA integrity index to monitor the response of TVT to vincristine and compare them with lysyl oxidase activity. Plasma and sera were collected before drug administration within four weeks from fifteen male dogs. The analytical method was mainly based on quantitative polymerase chain reaction for short and long cfDNA, and lysyl oxidase activity was measured in serum. Results: The results of cfDNA integrity index showed significant ( p<0.05 ) difference in a baseline to 2 nd and 3 rd week (with cut-off value 1.118 and 93.33% specificity). We found that the cfDNA integrity index was increased during weeks due to the reduction of shorts cfDNA in the 1 st week after treatment. lysyl Oxidase activity was increased during the 4 th week ( p<0.001 ) but there were no significant differences in the other weeks compared to baseline. ROC analysis of lysyl Oxidase revealed high sensitivity (100%) and specificity (93%) 2 nd , 3 rd weeks on comparison between Baseline. Multivariate analysis between cfDNA integrity index and lysyl Oxidase showed significant correlation ( p<0.05 ) only baseline results. Conclusions: Taken together, we propose short cfDNA, cfDNA integrity index, and lysyl Oxidase activity as a diagnostic biomarker and a putative prognostic candidate in TVT patients. These biomarkers could be used simultaneously for quickly diagnose TVT in combination with cytology.