Nonendoscopic Detection of Barrett’s Esophagus Using Methylated DNA Markers

Currently, an upper GI endoscopy with biopsies of the columnar-lined distal esophagus is necessary to diagnose Barrett’s esophagus (BE). Easier, noninvasive, nonendoscopy-based testing techniques have been identified for this precancerous condition. This prospective case-control study evaluated the performance of methylated DNA markers (MDMs) for detecting BE from mucosal cells obtained by a swallowed device.

Subjects with and without BE (cases vs controls) swallowed a sponge-on-string (SOS) device that was withdrawn after 8 minutes of ingestion. The cells from the sponge were collected, and DNA was extracted and evaluated for a panel of MDMs (ZNF568, BMP3, NDRG4, VAV3, ZNF682). The study included 199 subjects (110 cases: 83% male, mean age of 62 years, and 89 controls: 47% male, mean age of 60 years) in a training set to calibrate the MDM panel and, thereafter, 60 cases (83% male, mean age of 65 years) and 29 controls (48% male, mean age of 62 years) in a test set to evaluate the MDM panel against the current gold standard (upper endoscopy and biopsy). 

The sensitivity, specificity, and area under the curve (AUC) were 93%, 90%, and 96%, respectively, for the training set and 93%, 93%, and 97%, respectively, for the test set. At a prespecified specificity of 90% in the test set, the 5-MDM panel showed a sensitivity of 94%, 96%, and 86% to 100% for the detection of nondysplastic BE, any BE dysplasia, and BE neoplasia (high-grade dysplasia or early esophageal adenocarcinoma). The authors performed a 3-panel MDM (10 possible combinations of 3 MDMs) as well, and the specificity, sensitivity, and AUC were 92% to 93%, 89% to 92%, and 95% to 97%, respectively. The patients rated the tolerability of the SOS device-based procedure at a mean score of 2.2 (score range 0-10), and no major complications were noted.