A newly developed liquid biopsy assay accurately identified patients with Barrett’s esophagus and esophageal adenocarcinoma, researchers from a large international collaboration reported in Gut (2025;74[2]:169-181). The six-microRNA   signature demonstrated high accuracy in distinguishing patients with disease from controls, with an area under the receiver operating characteristic curve of 91.9%.

“The EMERALD blood test could enrich the toolkit of methods available for EAC screening,” the study authors wrote, which was led by Jinsei Miyoshi, MD, PhD, a researcher at the Center for Gastrointestinal Research, Baylor University Medical Center, in Dallas.

The international multicenter biomarker study involved 792 patient samples from four countries. The researchers systematically analyzed these samples and identified a signature of six microRNAs (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93), which they named EMERALD, that were consistently overexpressed in the serum of patients with BE and EAC.

To validate the accuracy of the signature, they analyzed samples from cohorts of 457 individuals with or without BE or EAC. The patients were a median of 63 years of age, approximately 60% were male, and 90% had an ECOG Performance Status of 0 or 1.

According to Dr. Miyoshi’s team, the EMERALD signature detected EAC with 84.0% sensitivity (95% CI, 76.6%-90.4%) and 90.5% specificity (95% CI, 81.7%-95.3%). The test also detected BE with 80.6% sensitivity (95% CI, 71.7%-87.2%).

Among those with BE and gastroesophageal reflux disease, the assay achieved a sensitivity of 92.8% and specificity of 85.1%. The test maintained robust specificity across different symptomatic control groups: 93.6% for patients with long-standing or refractory heartburn, 94.9% for those with dysphagia/odynophagia or regurgitation, and 98.0% for those with epigastralgia.

For early-stage disease detection in the training cohort, EMERALD was 95.7% sensitive, while it was 95.7% sensitive for carcinoma in situ, 100% sensitive for stage I and 92.0% for stage II EAC.

When distinguishing precancerous lesions from symptomatic non-BE controls with GERD, the liquid biopsy achieved an area under the curve of 94.8% (95% CI, 91.3%-98.2%).

Statistical analysis confirmed that higher EMERALD scores correlated with progressively increasing odds of having disease.

The authors estimated that EMERALD-based screening every five years could offer a cost-effective strategy to reduce EAC mortality and incidence compared with endoscopy every 10 years or no screening.

“While the training cohort primarily consisted of patients with early stage or in situ [EAC], the testing cohort also included a significant number of patients with precancerous lesions,” Dr. Miyoshi and his co-investigators noted. “Despite this compositional difference, patients with either EAC or precancerous lesions consistently displayed higher EMERALD values compared with non-disease controls in both cohorts.”

The investigators said while EMERALD could be a complementary tool to improve screening compliance and early detection of EAC and its precursor lesions, prospective studies are needed to validate these findings in a screening population.

—David Wild

Dr. Miyoshi reported no relevant financial disclosures.