P006 MiR-192 is associated with stricturing phenotype in Crohn’s disease
Cristina, T.(1);Mateescu, B.(2);Mitroi, A.(3);Cozaru, G.(3);Brinzan, C.(3);State, M.(2);Dumitru, A.(1);Rafti, R.(1);Dina, E.(1);Alexandrescu, L.(1);Dumitru, E.(1);
(1)County Clinical Emergency Hospital of Constanta, Gastroenterology, Constanta, Romania;(2)Clinical Hospital Colentina Bucharest, Gastroenterology, Bucharest, Romania;(3)County Clinical Emergency Hospital of Constanta, Genetics, Constanta, Romania;
Background
MicroRNAs (miRNAs) are small, non-coding short (ribonucleic acid) RNAs that have a role in the regulation of genes and protein expression. MiRNAs have altered expression in multiple autoimmune disorders including inflammatory bowel diseases (IBD). This emerging role has led to investigations into miRNA expression profiles in IBD to understand the pathogenesis of these diseases and lead to clinical advances in this area. Due to shared pathways in fibrosis, miRNAs that have a potential role in intestinal fibrosis are worthy of investigation, and miR-192 seems to be associated with fibrosis and strictures in Crohn’s disease (CD). The study aimed to assess the expression levels of tissue and circulating miR-192 in patients with CD.
Methods
The study included 58 patients with CD and 31 subjects as controls for the validation cohort. Demographic and clinical data (including phenotype of the disease), biomarkers: fecal calprotectin (fCal), endoscopy data: Short Endoscopic Score of Crohn’s disease (SES-CD), the expression levels of miR-192 in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic (ROC) analysis was performed to assess the miR-192 expression level as a potential biomarker for stricturing phenotype of CD.
Results
The mean fCal was 345+/- 112 μg/g. The mean SES-CD was 3.4 +/- 1.1. Regarding disease phenotype, 26 (44.8%) had inflammatory phenotype, 32 (55.2%) had stricturing phenotype, and no patient had penetrant phenotype . Regarding location, 20 (34.5%) were ileal, 5 (8.7%) were colonic, and 33 (56.8%) were ileocolic. Strictures were all located in the terminal ileum. The expression level of miR-192 was significantly upregulated in CD tissue samples compared to the control tissue samples only in the patients with stricturing phenotype (8.27 ± 2.87 vs. 4.20 ± 1.94; p < 0.01), whereas in inflammatory phenotype miR-192 was downregulated (-3.47 ± 1.02 vs. - 4.30 ± 0.84; p < 0.01). Similarly, serum miR-31 expression level in CD patients was significantly upregulated than in control serum samples only in the patients with stricturing phenotype (4.07 ± 1.00 vs. 1.55 ± 0.91; p < 0.01), whereas in inflammatory phenotype miR-192 was downregulated (- 0.25 ± 0.79 vs. 0.76 ± 0.83; p < 0.01). There was a strong correlation between tissue and circulating miR-192 with stricturing phenotype (r = 0.89, r = 0.85, p < 0.05). ROC analysis revealed that the expression level of miR-192 could help to discriminate stricturing CD patients from other phenotypes with very good specificity and sensitivity.
Conclusion
MiR-192 is associated with stricturing phenotype in CD and could be a biomarker of intestinal fibrosis. Furthermore, circulating miR-192 could be a non-invasive biomarker of intestinal fibrosis.