Salivary microRNAs in pediatric eosinophilic esophagitis

Abstract

Background: Diagnosis and management of eosinophilic esophagitis (EoE) occur via esophagogastroduodenoscopy with tissue biopsy. Objective: We sought to determine if salivary microribonucleic acid (miRNA) levels could differentiate children with EoE, serving as a noninvasive biomarker. Methods: Saliva was collected from children undergoing esophagogastroduodenoscopy (N = 291). miRNA analysis was conducted on 150 samples: EoE (n = 50), no pathologic alteration (n = 100). RNA was quantified with high throughput sequencing and aligned to build hg38 of the human genome using sequencing and alignment software. Quantile normalized levels of robustly expressed miRNAs (raw counts > 10 in 10% of samples) were compared across EoE and non-EoE groups with Wilcoxon rank sum testing. miRNA biomarker candidates were selected based on variable importance projection (VIP) scoring with partial least squared discriminant analysis (VIP > 1.5). Ability of these miRNAs to differentiate EoE status was assessed via logistic regression. Putative biologic targets for the miRNA candidates were determined in miRNA pathway analysis software. Results: Of the 56 salivary miRNAs reliably detected, miR-205-5p displayed the largest difference between EoE and non-EoE groups (V = 1623, adjusted p = 0.029). Six miRNAs (miR-26b-5p, miR-27b-3p, Let-7i-5p, miR-142-5p, miR-30a-5p, miR-205-5p) displayed elevated VIP scores (>1.5) and were able to differentiate EoE samples on logistic regression analysis with 70% sensitivity and 68% specificity. These six miRNAs demonstrated significant enrichment for gene targets involved in valine, leucine, and isoleucine biosynthesis (p = 0.0012), 2-oxycarboxylic acid metabolism (p = 0.043), and steroid hormone biosynthesis (p = 0.048). Conclusions: Salivary miRNAs represent a noninvasive, biologically relevant measure that may aid disease monitoring of EoE.