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

Janne G Lyngby, Marta Gòdia, Louise Brogaard, Annemarie T Kristensen, Merete Fredholm, Ellen Skancke, Joanna Morris, Nana Dupont, Silke Salavati Schmitz, David Argyle, Armand Sánchez, Charlotte R Bjørnvad, Susanna Cirera, Lise N Nielsen

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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.

Original languageEnglish
JournalJournal of Veterinary Internal Medicine
Volume36
Issue number6
Pages (from-to)1989-2001
ISSN0891-6640
DOIs
Publication statusPublished - 2022

Bibliographical note

© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.

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