Utility of Urinary miRNA Biomarkers for Canine Urothelial Carcinoma Diagnostics

Abstract

Urothelial carcinoma (UC) is one of the most frequent tumors in dogs. Besides cytology, histology, and testing for a BRAF mutation, non-invasive biomarkers would benefit the early detection and therapy of UC. This study aimed to compare the detectability of miRNAs in urine sediment and supernatant and to assess their potential as biomarkers for UC. The study involved two phases with 47 canine samples in total; in a pilot trial, ten different miRNAs (miR-16, 21, 103b, 106b, 146, 155, 182, 221, 222, and 375) were isolated from the urine sediments and supernatants from seven healthy control dogs and seven dogs with UC. In a further step, eight miRNAs were isolated from urine sediments from 18 healthy dogs, 11 dogs with purulent cystitis, and 18 dogs with UC. The detectability of miRNAs was improved when isolated from the urine sediment compared with the supernatant. MiR-16 was not deregulated, and miR-106b showed significantly lower expression in cystitis compared with the control. Lower copy numbers were seen for miR-21, 182, 221, and 222 in cystitis cases compared with the controls and UC, respectively. Deregulation was observed for miR-155 and miR-375 between all three groups. A panel including miR-182, 221, 222, 155, and 375 has the potential to discriminate among all three groups in a two-step approach.