MicroRNAs in Plasma-Derived Extracellular Vesicles as Non-Invasive Biomarkers for Eosinophilic Esophagitis

• Published in: International journal of molecular sciences Vol. 26; no. 2; p. 639
• Main Authors: Grueso-Navarro, Elena, Rodríguez-Alcolado, Leticia, Arias-González, Laura, Aransay, Ana M., Lozano, Juan-José, Sidorova, Julia, Juárez-Tosina, Rocío, González-Cervera, Jesús, Lucendo, Alfredo J., Laserna-Mendieta, Emilio J.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.01.2025; MDPI
• Subjects: Adult; Biological markers; Biomarkers; Biomarkers - blood; Biopsy; Case-Control Studies; Clinical medicine; Disease; Endoscopy; Eosinophilic Esophagitis - blood; Eosinophilic Esophagitis - diagnosis; Eosinophilic Esophagitis - genetics; Esophagitis; Esophagus; Extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Female; Gastroesophageal reflux; Genes; Health care expenditures; Humans; Inflammation; Male; Medical diagnosis; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; Patients; Plasma; Prospective Studies; Young Adult; United States; California; Spain; RNA sequencing; eosinophilic esophagitis (EoE); extracellular vesicles (EVs); liquid biopsy; microRNAs (miRNAs); non-invasive biomarker
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms26020639

Eosinophilic esophagitis (EoE) is a chronic inflammatory esophageal disorder. The lack of non-invasive biomarkers currently results in dependency on endoscopy with biopsies for its diagnosis and monitoring. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). This was a prospective single-center observational study of a discovery cohort of EoE patients (n = 26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx) and control subjects (n = 16). Small-RNA-seq was performed to identify differentially regulated small RNAs (sRNAs). Candidate miRNAs were validated in an independent cohort (EoE patients, n = 33; controls, n = 14). The pEVs-sRNA cargo differed among conditions. Compared with controls, Ser_Comb_22, Leu_Comb_5, miR-10b-5p, and miR-125a-5p were upregulated in EoE.Basal, and miR-224-5p, miR-221-3p, let-7d-5p, and miR-191-5p were downregulated. The combination of miR-221-3p and miR-10b-5p showed the best diagnostic performance. Comparing paired EoE samples, miR-374a-5p and miR-30a-3p were upregulated in EoE.Basal, while miR-15a-5p and let-7d-5p were downregulated. Combined miR-30a-3p and miR-15a-5p showed the best AUC values, and miR-30a-3p alone was best as a monitoring biomarker (p = 0.001). In conclusion, pEVs-sRNA changed upon inflammation in EoE patients, and miR-30a-3p was proposed as a potential biomarker for monitoring the treatment. This study was the first to explore the use of pEVs as a non-invasive biomarker for EoE.