TY - JOUR
T1 - Validation of a methylated DNA marker panel for the nonendoscopic detection of Barrett's esophagus in a multisite case-control study
AU - Iyer, Prasad G.
AU - Taylor, William R.
AU - Slettedahl, Seth W.
AU - Lansing, Ramona L.
AU - Hemminger, Lois L.
AU - Cayer, Frances K.
AU - Mahoney, Douglas W.
AU - Giakoumopoulos, Maria
AU - Allawi, Hatim T.
AU - Wu, Tsung Teh
AU - Wang, Kenneth K.
AU - Wolfsen, Herbert C.
AU - Antpack, Eduardo
AU - Kisiel, John B.
N1 - Funding Information:
In loving memory of Dr David A. Ahlquist, who inspired this work. DISCLOSURE: The following authors received research support for this study from the National Cancer Institute: J. B. Kisiel (CA214679); P. G. Iyer, J. B. Kisiel (CA241164). In addition, the following authors disclosed financial relationships: P. G. Iyer: Research funding from Exact Sciences, Pentax Medical, and Medtronic; consultant for Medtronic and Symple Surgical. W. R. Taylor, D. W. Mahoney: Co-inventor of Mayo Clinic intellectual property licensed to Exact Sciences for which royalties are received and paid to Mayo Clinic. M. Giakoumopoulos, H. T. Allawi: Employee of Exact Sciences. K. K. Wang: Research funding from Nine Point Medical, C2 Therapeutics, Olympus, Medtronic, and Boston Scientific. H. C. Wolfsen: Research funding from Exact Sciences and Nine Point Medical. J. B. Kisiel: Research funding from Exact Sciences; co-inventor of Mayo Clinic intellectual property licensed to Exact Sciences for which royalties are received and paid to Mayo Clinic; S. W. Slettedahl: Part of salary covered by contractual agreement between Mayo Clinic and Exact Sciences for intellectual know-how. All other authors disclosed no financial relationships. Research support for this study was provided by Exact Sciences for materials, reagents, and blinded long-probe quantitative amplified signal assays.
Funding Information:
DISCLOSURE: The following authors received research support for this study from the National Cancer Institute: J. B. Kisiel (CA214679); P. G. Iyer, J. B. Kisiel (CA241164). In addition, the following authors disclosed financial relationships: P. G. Iyer: Research funding from Exact Sciences, Pentax Medical, and Medtronic; consultant for Medtronic and Symple Surgical. W. R. Taylor, D. W. Mahoney: Co-inventor of Mayo Clinic intellectual property licensed to Exact Sciences for which royalties are received and paid to Mayo Clinic. M. Giakoumopoulos, H. T. Allawi: Employee of Exact Sciences. K. K. Wang: Research funding from Nine Point Medical, C2 Therapeutics, Olympus, Medtronic, and Boston Scientific. H. C. Wolfsen: Research funding from Exact Sciences and Nine Point Medical. J. B. Kisiel: Research funding from Exact Sciences; co-inventor of Mayo Clinic intellectual property licensed to Exact Sciences for which royalties are received and paid to Mayo Clinic; S. W. Slettedahl: Part of salary covered by contractual agreement between Mayo Clinic and Exact Sciences for intellectual know-how. All other authors disclosed no financial relationships. Research support for this study was provided by Exact Sciences for materials, reagents, and blinded long-probe quantitative amplified signal assays.
Publisher Copyright:
© 2021 American Society for Gastrointestinal Endoscopy
PY - 2021/9
Y1 - 2021/9
N2 - Background and Aims: We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett's esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers. Methods: Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. 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 and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .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. (Clinical trial registration number: NCT 02560623.)
AB - Background and Aims: We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett's esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers. Methods: Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. 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 and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .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. (Clinical trial registration number: NCT 02560623.)
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U2 - 10.1016/j.gie.2021.03.937
DO - 10.1016/j.gie.2021.03.937
M3 - Article
C2 - 33857451
AN - SCOPUS:85108966543
SN - 0016-5107
VL - 94
SP - 498
EP - 505
JO - Gastrointestinal endoscopy
JF - Gastrointestinal endoscopy
IS - 3
ER -