Identification of Circulating MicroRNA Signatures in Crohn's Disease Using the Nanostring nCounter Technology

Abstract

Background: Current clinical indices, such as Harvey-Bradshaw index, are often inadequate for the assessment of disease activity in Crohn's disease (CD). Alternative methods including imaging modalities and laboratory markers, such as C-reactive protein (CRP), are routinely applied to assess disease activity. However, laboratory markers poorly reflect the actual disease activity. Consequently, novel biomarkers represent a clinical necessity for CD patient management. We hypothesized that circulating serum-derived microRNAs may be used as diagnosis and disease activity monitoring tools of CD patients. Methods: To test this hypothesis, we performed microRNA expression profiling through Nanostring nCounter technology in blood serum samples of CD patients and healthy control subjects. Harvey-Bradshaw index score was used to capture clinical disease activity; CRP was measured as part of standard clinical practice. The expression profile of circulating microRNAs and the levels of CRP correlated with Harvey-Bradshaw index. Results: We identified a signature of 10 circulating microRNAs that are differentially expressed in CD patients compared with healthy control subjects. Two of these microRNAs (hsa-miR-1286 and hsa-miR-1273d) correlated with CD disease activity and exhibited higher correlation values compared with CRP. Further analysis revealed distinct microRNA signatures between CD patients with ileal and colonic involvement. Conclusions: Circulating microRNAs show superior value as diagnostic and disease activity markers in comparison to traditional methods. Circulating microRNAs could improve CD patient management, if applied in combination with current state-of-the-art diagnostic and disease activity assessment modalities.