Circulating microRNA146b-5p is superior to C-reactive protein as a novel biomarker for monitoring inflammatory bowel disease

Abstract

Background: Owing to the importance of early treatment, simple and reliable methods for monitoring inflammatory bowel disease (IBD) are needed.

Aims: To determine whether circulating microRNAs are reliable biomarkers for IBD monitoring.

Methods: Serum levels of 17 candidate microRNAs were measured by quantitative real-time polymerase chain reaction in a discovery cohort (n = 120). Differentially expressed serum microRNAs were further investigated in an independent training cohort (n = 341). Correlations between relative microRNA levels and disease activity were evaluated. A disease control group was included to investigate the specificity of microRNA. Logistical regression was used to construct a microRNA classifier to identify endoscopic activity. Its predictive value was explored in the validation cohort (n = 66) using the area under the receiver operating characteristic curve (AUC).

Results: Serum microRNA146b-5p (miR-146b-5p) expression was 2.87- and 2.72-fold higher in patients with Crohn's disease and ulcerative colitis, respectively, than in healthy controls. Serum miR-146b-5p was significantly correlated with disease activity and was more specific than C-reactive protein (CRP). A classifier was built for Crohn's disease, ie P [Endoscopically active] = $\frac{1}{1+e^{2.937-0.737(miR-146b-5p)-0.008PLT}}$ , with a greater AUC of 0.869 [0.764-0.940] than that for CRP (0.680 [0.554-0.790]) (P = 0.0043).

Conclusions: MiR-146b-5p may better reflect mucosal inflammation in IBD than CRP. The Crohn's disease classifier developed in this study may be valuable for identifying endoscopic activity in patients with Crohn's disease.

Keywords: circulating biomarker; inflammatory bowel disease; microRNA classifier; microRNA-146b-5p.