Progress in methylated DNA markers for Barrett's detection

In order to be adopted widely, non-invasive technologies for detecting Barrett's esophagus (e.g., EsophaCap, Cytosponge) need a companion assay that is both accurate and inexpensive. Here Dr. Iyer at the Mayo Clinic and collaborators report promising results for a set of five methylated DNA markers.

Gastrointest Endosc. 2021 Apr 12;S0016-5107(21)01184-6.

doi: 10.1016/j.gie.2021.03.937.

Validation of a methylated DNA marker panel for the nonendoscopic detection of Barrett's esophagus in a multi-site case-control study

Prasad G. Iyer, William R. Taylor, Seth W. Slettedahl, Ramona L. Lansing, Lois L. Hemminger, Frances K. Cayer, Douglas W. Mahoney, Maria Giakoumopoulos, Hatim T. Allawi, Tsung-Teh Wu, Kenneth K. Wang, Herbert C. Wolfsen, Eduardo Antpack, John B. Kisiel,

Abstract:

Background and Aims

We previously identified a 5 methylated DNA marker (MDM) panel for nonendoscopic Barrett’s esophagus (BE) detection. In this study, we aimed to (1) recalibrate the performance of the 5 MDM marker panel using a simplified assay in a training cohort, (2) validate the panel in an independent test cohort, and (3) explore accuracy of an MDM panel with only 3 markers.

Methods

Participants were recruited from 3 medical centers. The SOS device (EsophaCap, CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and controls. A 5 MDM panel was blindly assayed using a simplified assay. Random forest modeling analysis was performed, in silico cross-validated in the training set, and then locked down, before test set analysis.

Results

The training set had 199 patients: 110 BE cases, 89 controls, and the test set had 89 patients: 60 BE cases and 29 controls. Sensitivity of the 5 marker panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under receiver operating characteristic curves were 0.96 and 0.97 in the training and test sets, respectively. Model accuracy was not influenced by age, sex, or smoking history. Multiple 3-MDM panels achieved similar accuracy.

Conclusions

A 5-MDM panel for BE is highly accurate in training and test sets in a blinded multisite case-control analysis using a simplified assay. This panel may be reduced to only 3 MDMs in the future.

Copyright © 2021 by the American Society for Gastrointestinal Endoscopy

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