Profiling microRNA and mRNA in Esophageal Biopsies of Patients with Eosinophilic Esophagitis before and after Treatment
Shaolei Lu, Kelly Cleveland, Vincent Mukkada, Shamlal Mangray, Christoph Schorl, Alexander Brodsky, Murray Resnick. The Warren Alpert Medical School of Brown University, Providence, RI
Background: Eosinophilic esophagitis (EoE) is a chronic eosinophil-predominant allergic process. The role of microRNAs (miRNAs) in the development and control of inflammation is an active area of ongoing research, however, the miRNA profile of EoE biospies has yet to be elucidated. The purpose of this study was to define the miRNA and mRNA profile of a well characterized group of pediatric EoE patients.
Design: Formalin fixed paraffin embedded mucosal biopsies were obtained from five EoE patients. Each patient was biopsied before and after successful treatment with a combination of acid suppression and steroids. The pre-treatment biopsies had all of the classic histologic features of EoE whereas the post-treament biopsies were essentially normal with rare intraepithelial eosinophils. The epithelial layer of the mucosa was dissected and the miRNA and mRNA was isolated and profiled using TaqMan MicroRNA Arrays and Affymetrix chips, respectively. The top miRNA candidates were further confirmed by quantitative RT-PCR on a new set of both paired (8) and unpaired (10) biopsies.
Results: Thirty eight miRNAs was found to be differentially regulated following treatment with a p-value of < 0.05. Most of them (23) were up-regulated in the disease state and down-regulated after treatment. All six top up-regulated miRNAs (miRNA-145, miRNA-146a, miRNA-146b, miRNA 142, miRNA 214 and miRNA21) were further validated using a new set of biopsy specimens. In addition mRNA analysis was performed and 112 mRNAs were found to be dysregulated by a factor of 4 or more. These included a number of genes previously described as being differentially regulated in EoE such as CCL-26, POSTN, CPA3, FLG and SPRR3 as well as a number of genes as yet to be described in EoE.
Conclusions: This study is the first to determine miRNA and mRNA profiles of EoE patients before and after therapy. We identified certain mRNAs and miRNAs that have been previously described to play a role in immune or allergic responses as well as a number of novel new targets. Future studies will focus on investigation of the interaction between these differentially regulated miRNAs and mRNAs as well as to confirm the role of those novel dysregulated genes in the pathogenesis of the inflammatory response.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 114, Monday Morning