Discovery of Methylated DNA Biomarkers for Potential Nonendoscopic Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

• Tác giả: Yousra Ahmed, Venkata Akshintala, Shahin Ayazi, Richard Battaforano, Karim Boudadi, Olaya Brewer, Kathy Bull-Henry, Vincent Castillo, Yulan Cheng, Leslie Cope, Josephine Feliciano, Zacharia H Foda, Rachel Ganster, Shayan Gheshlaghi, Jinny Ha, Russell Hales, Robert Hughes, Ken Hui, Simran Jit, Blair A Jobe, Andrew Kalra, Lisa Kann, Mouen Khashab, Vincent Lam, Sarah Laun, Daniel Lunz, Ke Ma, Michelle Ma, Kristin Marrone, Stephen J Meltzer, Saowanee Ngamruengphong, Eun Ji Shin, Vikesh K Singh, Manon Spaander, Alan H Tieu, Hua-Ling Tsai, Hao Wang, Yifan Yang, Ali H Zaidi, Pauline Zellenrath
• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.32 *Diseases of pharynx and esophagus
• Thông tin xuất bản: United States : The American journal of gastroenterology , 2025
• Bộ sưu tập: NCBI
• ID: 689671

Tóm tắt

 INTRODUCTION: We sought to develop a minimally invasive, robust, accessible nonendoscopic strategy to diagnose Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), and its immediate precursor lesion, high-grade dysplasia (HGD) based on methylated DNA biomarkers applied to a retrievable sponge-capsule device in a cohort representative of the BE population (i.e., mostly short-segment, nondysplastic BE [NDBE]). METHODS: We identified 12 candidate methylation markers to distinguish normal vs abnormal esophagus. These 12 markers were first assayed in 21-paired matched NDBE-normal esophageal tissues, then assessed in a case-control study of 234 esophageal samples collected using a sponge-capsule device. A classification algorithm was developed using the least absolute shrinkage and selection operator in a 199-patient training set and tested in an independent 35-patient test set. RESULTS: Twelve markers ( A1BG , C9orf50 , cg00720137 , FLI1 , GRAMD1B , HOXB13 , IRF4 , KCNQ3 , NTNG1 , SPX , TBC1D30 , and USP44 ) were significantly hypermethylated (i.e., all P <
  0.05) in BE vs matched normal esophageal biopsies. A discriminatory 3-gene least absolute shrinkage and selection operator panel ( USP44 , TBC1D30 , and NELL1 ), adjusted for age and sex, accurately distinguished HGD or EAC from normal control patients in both training (area under the receiver operating characteristic curve [AUC] 0.911, 95% confidence interval [CI] 0.863-0.959) and test (AUC 0.969, 95% CI 0.911-1.00) sets. In normal vs NDBE/LGD/HGD/EAC patients, this algorithm exhibited AUCs of 0.862 (95% CI 0.812-0.912) and 0.864 (95% CI 0.745-0.982) in training and test sets, respectively. In normal vs NDBE patients, the algorithm yielded AUCs of 0.819 (95% CI 0.748-0.889) and 0.776 (95% CI 0.583-0.968) in training and test sets, respectively. DISCUSSION: This discriminatory biomarker panel algorithm exemplifies a practical nonendoscopic strategy to diagnose BE, HGD, and EAC using a minimally invasive sponge-capsule device coupled with DNA methylation markers.