P021 Differential plasma microRNA expression profile in ulcerative colitis patients according to their response to corticosteroids
J.E. Naves*1, J. Manye1, 2, V. Loren1, M. Mañosa2, 3, A. García-Jaraquemada1, I. Moret2, 4, G. Bastida2, 4, B. Beltrán2, 4, E. Cabré2, 3, E. Domènech2, 3
1Germans Trias i Pujol Health Sciences Research Institute, Gastroenterology Department, Badalona, Spain, 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, , Spain, 3Hospital Universitari Germans Trias i Pujol, Gastroenterology Department, Badalona, Spain, 4Hospital La Fe, Gastroenterology Unit, Valencia, Spain
Corticosteroids (CS) remain the first line treatment for moderate and severe active ulcerative colitis (UC). However up to 40% of patients do not have an adequate response. We use clinical and biological variables to predict a bad response after three days of treatment, but to date we have not been able to predict response before starting therapy. MicroRNA (miR) are small non-coding RNA fragments that modulate gene expression at a post-transcriptional level, playing a critical role in many biological processes. In previous studies we found a differential miR profile in rectal mucosa of patients with UC responders and non-responders to CS. Objective: To compare the miR profile in plasma of patients with active UC responding and non-responding to CS.
Plasma samples were obtained from UC patients before CS treatment for a moderate-to-severe flare, and also from healthy controls. Patients were grouped according to clinical response (non-responder = moderate or severe activity according to Montreal's classification or need of rescue therapy at day 7; responder = mild activity or remission without rescue therapy at day 7). miR were identified on plasma samples by means of a sequencing method (Illumina kit). After the comparison between groups those miR with a fold change greater than 1.5 and adjusted p-value less than 0.05 were further studied. Potential targets of selected miR were checked in Target Human Scan and miRwalk database, and their impact on biological activity was searched in GeneCodis database.
10 healthy controls and 20 patients with UC (10 responders and 10 non responders to CS) were included. Comparison between responders and non-responders showed no significant differences. However, we found three miR with differential expression between healthy controls and non-responders (miR-1290, miR-4508, and miR-149-5p). In silico study of these miRNAs showed more than 1000 genes potentially regulated by each, mainly involved in MAPKinasa signaling pathway, regulation of cytoskeletum, calcium signaling pathway, and endocytosis.
The plasma miR profile obteined in the present study is not usefull to identify patients with active UC not responding to CS. However further studies integrating plasma and tissue miR profiles may help us to develop a potential biomarker of response to CS in UC.