Novel blood biomarkers as diagnostic and prognostic test in IBD:
Clinical decision and patient care management in inflammatory bowel diseases is largely based on the assessment of clinical symptoms, while the biomarkers currently in use poorly reflect the actual disease activity. Therefore, the identification of novel biomarkers will serve an unmet clinical need for IBD screening and patient management. We examined the utility of circulating microRNAs for diagnosis and disease activity monitoring in patients with ulcerative colitis (UC).
Our team identified a signature of 12 circulating microRNAs that differentiate patients with UC from control subjects. Moreover, 6 of these microRNAs significantly correlated with UC disease activity. Importantly, a set of 4 microRNAs (hsa-miR-4454, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-320e), which correlated with UC disease activity were found to have higher sensitivity and specificity values than C-reactive protein. Circulating microRNAs provide a novel diagnostic and prognostic marker for patients with UC. The use of an FDA-approved platform could accelerate the application of microRNA screening in a gastrointenstinal clinical setting. When used in combination with current diagnostic and disease activity assessment modalities, microRNAs could improve both IBD screening and care management.
Polytarchou C, Oikonomopoulos A, Joshi S, Touroutoglou A, Koukos G, Hommes DW, Iliopoulos D*. Assessment of circulating microRNAs for the diagnosis and disease activity evaluation in ulcerative colitis patients by using the Nanostring Technology. Inflamm Bowel Dis, 2015. *corresponding author
Novel therapeutic targets and drugs in pediatric and adult IBD
MicroRNAs are non-coding RNA molecules, 18-25 nucleotides long that suppress gene expression in the post-transcriptional level, through binding in the 3’ untranslational region (UTR) of their target genes. MicroRNAs have been involved in the pathogenesis of different human diseases and recent studies have shown that targeting microRNAs could have therapeutic potential. Our research has evaluated the role of microRNAs, in the early days of this research field, in different human diseases, including IBD. Specifically, we have identified that microRNAs regulate the inflammatory response in both pediatric and adult patients with ulcerative colitis. Furthermore, we found that microRNAs are key factors related with the progression of ulcerative colitis and development of colon cancer. Importantly, we have developed a chemical inhibitor of miR-214 that suppresses ulcerative colitis development and colon cancer tumor growth in mice. Based on these data, we are planning to perform all the required pre-IND studies, aiming for a phase I clinical trial during 2017.
A. Polytarchou C, Hommes DW, Palumbo T, Hatziapostolou M, Koutsioumpa M, Koukos G, van der Meulen-de Jong AE, Oikonomopoulos A, van Deen WK, Vorvis C, Serebrennikova OB, Birli E, Choi J, Chang L, Anton PA, Tsichlis PN, Pothoulakis C, Verspaget HW, Iliopoulos D. MicroRNA214 is associated with progression of ulcerative colitis and inhibition reduces development of colitis and colitis-associated cancer in mice. Gastroenterology, 2015.
B. Koukos G, Polytarchou C, Kaplan JL, Oikonomopoulos A, Ziring D, Hommes DW, Wahed R, Kokkotou E, Pothoulakis C, Winter HS, Iliopoulos D*. A microRNA signature in pediatric ulcerative colitis: deregulation of the miR-4284/CXCL5 pathway in the intestinal epithelium. Inflamm Bowel Dis, 212: 996-1005, 2015. *corresponding author
C. Koukos G, Polytarchou C, Kaplan JL, Morley-Fletcher A, Gras-Miralles B, Kokkotou E, Baril-Dore M, Pothoulakis C, Winter HS, Iliopoulos D. MicroRNA-124 regulates STAT3 expression and is downregulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology, 2013; 145:842-52.
D. Law IK, Bakirtzi K, Polytarchou C, Oikonomopoulos A, Hommes D, Iliopoulos D, Pothoulakis C. Neurotensin-regulated miR-133a is involved in proinflammatory signaling in human colonic epithelial cells and in experimental colitis. Gut, 2014.