P096 Specific plasma micro-RNA profiles for prediction of recurrence in Crohn’s disease in pre-surgery and established recurrence scenarios

Abstract

Abstract Background Crohn’s disease (CD) patients who undergo ileocolonic resection are at high risk of postoperative recurrence (POR). Both environmental and genetic factors are known to influence CD pathogenesis. MicroRNAs (miRs) are important epigenetic regulators in CD, but their role in the progression to POR is still unknown. Thus, we aimed to identify differential miRs profiles and their potential use to predict POR in CD patients. Methods A cohort of 33 CD patients who underwent a resection was consecutively and prospectively followed for at least 1 year. Patients were classified according to the presence or absence of POR during the follow-up. POR was assessed by ileocolonoscopy (Rutgeerts’ index ≥ i2b) or MRI enterography within 6–12 months after surgery. Patients received postoperative therapy to prevent POR (thiopurines 47%; anti-TNFα 25%; mesalamine 9%; combination therapy 3%; none 16%). Peripheral blood samples were taken at fixed times. Total RNA was obtained from miRNeasy Serum/Plasma Advanced Kit (Qiagen) and run on the miRCURY LNAtm Universal RT microRNA PCR with a miRs panel selection (32) based on previous experiments. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves with the R software. Results MicroRNAs profiles were studied at two different times: presurgery (PS) and at the time of the morphological POR or, in those who remained in remission, 1 year after surgery (1 year). The miRs whose fluorescent signal did not differ from background noise were excluded from the analysis [8 in PS (25%); 5 in 1 year (16%)]. Using elastic net regression, five miRs (hsa.miR.191.5p, hsa.miR.15b.5p, hsa.miR.106b.5p, hsa.miR.451a and hsa.miR.93.5p) were selected for discriminating the two patient groups at the time pre-surgery. Seven miRs (hsa.miR.15b.5p, hsa.miR.126.3p, hsa.miR.451a, hsa.let.7b.5p, hsa.miR.93.5p, hsa.miR.423.5p and hsa.miR.125b.5p) were selected for discriminating the two patient groups at the time of 1 year. Using a predictive model with these miRs, an overall AUC of 0.86 (95% confidence interval, 0.75–0.97) was achieved for PS, and 0.96 (0.92–1.0) for 1 year. Conclusion This study shows that plasma microRNAs are useful biomarkers in the POR scenario. When recurrence is already established, a group of plasma miRs is also specifically expressed, thus assessing them could prevent patients from receiving and endoscopic procedure for POR evaluation. Furthermore, microRNA assessment PS could predict which patients will develop recurrence within 1 year of surgery. This could also have an impact on clinical management, selecting patients who can avoid immunosuppressive treatment and the ones who may need more intensive therapeutic strategies.