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

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Abstract

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).

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Acknowledgements

We thank Ms. Maki Nomura (Kawasaki Medical School, Okayama, Japan) and Mr. Takuya Wada (Kinki University Faculty of Medicine, Osaka, Japan) for assistance with the laboratory work.

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Authors and Affiliations

  1. Division of Gastroenterology Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama Prefecture, 701-0192, Japan

    Kyosuke Goda, Takahisa Murao, Yukiko Handa, Ryo Katsumata, Shinya Fukushima, Rui Nakato, Motoyasu Osawa, Manabu Ishii, Minoru Fujita, Osamu Handa, Hiroshi Matsumoto, Eiji Umegaki & Akiko Shiotani

  2. Department of Genome Biology, Kindai University, Faculty of Medicine, Osaka, Japan

    Yoshihiko Fujita & Kazuto Nishio

  3. Division of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, FL, USA

    Timothy M. Wallace, Herbert C. Wolfsen & Michael B. Wallace

  4. Division of Digestive Diseases and Nutrition, The Carol and Frank Morsani Center, Tampa, FL, USA

    Rene Gomez-Esquivel

  5. Division of Gastroenterology, Mount Sinai Medical Center, Miami Beach, FL, USA

    Manuel Berzosa

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  1. Kyosuke Goda
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  2. Takahisa Murao
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  9. Minoru Fujita
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  16. Manuel Berzosa
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  17. Herbert C. Wolfsen
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  18. Michael B. Wallace
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  19. Eiji Umegaki
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  20. Akiko Shiotani
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Corresponding author

Correspondence to Kyosuke Goda.

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Ethical statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

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Informed consent or substitute for it was obtained from all patients for being included in the study.

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Goda, K., Murao, T., Handa, Y. et al. Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy. Esophagus 18, 306–314 (2021). https://doi.org/10.1007/s10388-020-00762-5

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