Analysis of Salivary MicroRNAs in Pediatric Eosinophilic Esophagitis

Diagnosis and management of eosinophilic esophagitis (EoE) occur esophagogastroduodenoscopy with tissue biopsy. We sought to determine if salivary microribonucleic acid (miRNA) levels could differentiate children with EoE, serving as a noninvasive biomarker. 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 logistic regression. Putative biologic targets for the miRNA candidates were determined in miRNA pathway analysis software. 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). Salivary miRNAs represent a noninvasive, biologically relevant measure that may aid disease monitoring of EoE.