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. 2025 Jun 27;12(7):621.
doi: 10.3390/vetsci12070621.

Utility of Urinary miRNA Biomarkers for Canine Urothelial Carcinoma Diagnostics

Alexandra Kehl  1   2 , Heike Aupperle-Lellbach  1   2 , Maria Brockmann  1 , Anna-Lena van de Weyer  1 , Marielle Appenzeller  1 , Katja Steiger  2
Affiliations

Utility of Urinary miRNA Biomarkers for Canine Urothelial Carcinoma Diagnostics

Alexandra Kehl et al. Vet Sci. .

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.

Keywords: biomarker; cystitis; dog; miRNA; urine; urothelial carcinoma.

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Conflict of interest statement

Authors A.K., H.A.-L., M.B., A.-L.v.d.W., and M.A. were employed by the company LABOKLIN GmbH&Co.KG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
Examples of the cytological pictures from urine sediments of the groups: cell-poor control (A), severe purulent cystitis with bacteria (B), and urothelial carcinoma (C) (bar = 50 µm).
Figure 2
Figure 2
Normalized expression levels of miR-16 (A), 106b (B), 21 (C), 182 (D), 221 (E), 222 (F), 155 (G), and 375 (H) in different groups (control, cystitis, and carcinoma). The absolute miRNA copy number was related to the internal normalizer RNU6B. The results are shown as normalized expression values with a log 10 scale. * p < 0.05, ** p < 0.001. Green—control; blue—cystitis; red—carcinoma. The scales are not consistent but adjusted for clearer presentation.
Figure 3
Figure 3
Receiver operating curve (ROC) analysis of analyzed miRNAs with combined control/carcinoma vs. cystitis. Sensitivity is plotted against specificity on a graph. A diagonal line on this graph indicates random guessing. Any points above this line represent good classification. The ideal prediction method is found near the upper left corner, resulting in an area under the curve (AUC) > 0.9.
Figure 4
Figure 4
Receiver operating curve (ROC) analysis of analyzed miRNAs with control vs. carcinoma. Sensitivity is plotted against specificity on a graph. A diagonal line on this graph indicates random guessing. Any points above this line represent good classification. The ideal prediction method is found near the upper left corner, resulting in an area under the curve (AUC) > 0.9.
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