Candidate circulating microRNA biomarkers in dogs with chronic pancreatitis

Background: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis. Hypothesis: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers. Animals: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17). Methods: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, mouse, and human genomes. Differentially expressed microRNAs were identified and the potential mechanistic relevance explored using Qiagen Ingenuity Pathway Analysis (IPA). Results: Reads mapping to 196 mature microRNA sequences were detected. Eight circulating microRNAs were significantly differentially expressed in dogs with pancreatitis (>= 2-fold change and false discovery rate <0.05). Four of these mapped to the canine genome (cfa-miR-221, cfa-miR-222, cfa-miR-23a, and cfa-miR-205). Three mapped to the murine genome (mmu-miR-484, mmu-miR-6240, mmu-miR-101a-3p) and 1 to the human genome (hsa-miR-1290). Expression in dogs with pancreatitis was higher for 7 microRNAs and lower for mmu-miR-101a-3p. Qiagen IPA demonstrated a number of the differently expressed microRNAs are involved in a common pancreatic inflammatory pathway. Conclusions: The significantly differentially expressed microRNAs represent promising candidates for further validation as diagnostic biomarkers for canine pancreatitis.