Association of fecal and serum microRNA profiles with gastrointestinal cancer and chronic inflammatory enteropathy in dogs.

ABSTRACT

BACKGROUND: Reliable biomarkers to differentiate gastrointestinal cancer (GIC) from chronic inflammatory enteropathy (CIE) in dogs are needed. Fecal and serum microRNAs (miRNAs) have been proposed as diagnostic and prognostic markers of GI disease in humans and dogs. HYPOTHESIS/OBJECTIVES: Dogs with GIC have fecal and serum miRNA profiles that differ from those of dogs with CIE. AIMS: (a) identify miRNAs that differentiate GIC from CIE, (b) use high-throughput reverse transcription quantitative real-time PCR (RT-qPCR) to establish fecal and serum miRNA panels to distinguish GIC from CIE in dogs. ANIMALS Twenty-four dogs with GIC, 10 dogs with CIE, and 10 healthy dogs, all client-owned. METHODS: An international multicenter observational prospective case-control study. Small RNA sequencing was used to identify fecal and serum miRNAs, and RT-qPCR was used to establish fecal and serum miRNA panels with the potential to distinguish GIC from CIE. RESULTS: The best diagnostic performance for distinguishing GIC from CIE was fecal miR-451 (AUC 0.955, sensitivity 86.4%, specificity 100%), miR-223 (AUC 0.918, sensitivity 90.9%, specificity 80%), and miR-27a (AUC 0.868, sensitivity 81.8%, specificity 90%) and serum miR-20b (AUC 0.905, sensitivity 90.5%, specificity 90%), miR-148a-3p (AUC 0.924, sensitivity 85.7%, specificity 90%), and miR-652 (AUC 0.943, sensitivity 90.5%, specificity 90%). Slightly improved diagnostic performance was achieved when combining fecal miR-451 and miR-223 (AUC 0.973, sensitivity 95.5%, specificity 90%). CONCLUSIONS AND CLINICAL IMPORTANCE When used as part of a diagnostic RT-qPCR panel, the abovementioned miRNAs have the potential to function as noninvasive biomarkers for the differentiation of GIC and CIE in dogs.