Esophagus to Small Intestine
Gut. 2025;74(2):169-181
Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: The EMERALD multicentre study
Background: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s oesophagus (BE).
Objective: To develop and test a blood-based assay for EAC and BE.
Design: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia (EMERALD) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n = 134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). The authors finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs from a training cohort (n = 160) and independently tested it in an external cohort (n = 295).
Results: After a strict process of biomarker discovery and selection, the authors identified 6 miRNAs that were overexpressed in all sera of patients compared with non-disease controls from 3 independent cohorts of different nationalities (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93). They established a 6-miRNA diagnostic signature using the training cohort (area under the receiver operating characteristic curve [AUROC], 97.6%) and tested it in an independent cohort (AUROC, 91.9%). This assay could also identify patients with BE among patients with gastro-oesophageal reflux disease (AUROC, 94.8%, sensitivity, 92.8%, specificity, 85.1%).
Conclusion: Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, the authors have developed and validated a novel blood test that might complement screening options for Barrett’s oesophagus/oesophageal adenocarcinoma.