Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy

• Published in: Esophagus : official journal of the Japan Esophageal Society Vol. 18; no. 2; pp. 306 - 314
• Main Authors: Goda, Kyosuke, Murao, Takahisa, Handa, Yukiko, Katsumata, Ryo, Fukushima, Shinya, Nakato, Rui, Osawa, Motoyasu, Ishii, Manabu, Fujita, Minoru, Handa, Osamu, Matsumoto, Hiroshi, Fujita, Yoshihiko, Nishio, Kazuto, Wallace, Timothy M., Gomez-Esquivel, Rene, Berzosa, Manuel, Wolfsen, Herbert C., Wallace, Michael B., Umegaki, Eiji, Shiotani, Akiko
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.04.2021; Springer Nature B.V
• Subjects: Adenocarcinoma - pathology; Barrett Esophagus - diagnosis; Biomarkers; Endoscopy; Endoscopy, Gastrointestinal; Esophageal cancer; Esophageal Neoplasms - pathology; Esophagus; Gastroenterology; Humans; Medical diagnosis; Medicine; Medicine & Public Health; Metabolism; Molecular biology; Original Article; Surgical Oncology; Thoracic Surgery; United States; United States; Biomarkers; Barrett’s esophagus; Narrow-band imaging; Esophageal adenocarcinoma; Magnifying endoscopy
• ISSN: 1612-9059; 1612-9067
• DOI: 10.1007/s10388-020-00762-5

Background Barrett’s esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. Methods In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. Results Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase ( MMP ) family associated with ‘collagen metabolic process’ and ‘multicellular organismal macromolecule metabolic process’ as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors ( DAF and CD55 ) and topoisomerase type Iiα ( TOP2A ), and down-regulated expression of the sodium channel epithelial 1 beta subunit ( SCNN1B ). Conclusions The up-regulation of CD55 and TOP2A , and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. Trial registration University Hospital Medical Information Network (UMIN) (000004004).