Pathogenetic analysis of esophageal Barrett's adenocarcinoma from genetic and functional aspects.

• Project/Area Number: 19K17451
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Chiba University
• Principal Investigator: Okimoto Kenichiro 千葉大学, 医学部附属病院, 助教 (30770739)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 食道バレット腺癌 / NGS / バレット食道腺癌

Outline of Research at the Start

本研究ではバレット食道（BE）、バレット食道腺癌（EAC）に対して食道機能評価及び遺伝子学的解析を行い、EACの病態を明らかにし、早期発見、治療に結びつける事を目指す。１）次世代シークエンサー、免疫組織学的染色による解析
2）食道機能評価により研究を遂行する。前者に関しては食道癌に特徴的な遺伝子座を含むパネルを使用し、BE、EACの遺伝子変異を同定する。また免疫組織学的染色を行い主要遺伝子の変異が認められる発現の程度、局在を明らかにする。後者に関しては食道下部への胃逆流の解析、食道内圧検査、食道粘膜バリア機能評価から、胃逆流、粘膜バリア機能とBE、EACとの関係を解析する。

Outline of Final Research Achievements

The SSBE group consisted of 12 patients and 12 lesions, the Long segment BE (LSBE) group consisted of 12 patients and 12 lesions, and the EAC group　consisted of 9 patients and 11 lesions (3 EMRC and 8 ESD), for a total of 33 patients and 35 lesions treated endoscopically. Only the cancerous area was cut out by dissection. Somatic mutations were identified after DNA extraction from each sample. Conclusion: A putative driver of TP53 was found in two SSBEs
(16.7%). It is suggested that SSBEs that are not suspected to be atypical by conventional endoscopic observation may have carcinogenic potential, and require careful follow-up.The results of this study suggest the need for further investigation.

Academic Significance and Societal Importance of the Research Achievements

上記研究内容を論文化しGenetic profiles of Barrett's esophagus and esophageal adenocarcinoma in Japanese patientsとして報告した(Sci Rep. 2021 Sep 3;11(1):17671)
本研究により比較的有病率が低いとされてきた本邦におけるバレット食道腺癌の遺伝学的背景がある程度明らかにされた。欧米と類似したプロファイルを呈する事が分かり、今後さらに増加していく傾向になるかもしれない事が示唆された.

Research Products

• [Journal Article] Genetic profiles of Barrett’s esophagus and esophageal adenocarcinoma in Japanese patients (2021)
  • Author(s): Tokunaga Mamoru、Okimoto Kenichiro、Akizue Naoki、Ishikawa Kentaro、Hirotsu Yosuke、Amemiya Kenji、Ota Masayuki、Matsusaka Keisuke、et al.
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 17671-17671
  • DOI: 10.1038/s41598-021-97249-9
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive Analysis of Barrett's Esophagus: Focused on Carcinogenic Potential for Barrett's Cancer in Japanese Patients (2020)
  • Author(s): Kentaro Ishikawa , Kenichiro Okimoto, et al.
  • Journal Title: Dig Dis Sci . Volume: epub ahead of printing Issue: 8 Pages: 2674-2681
  • DOI: 10.1007/s10620-020-06563-1
  • Peer Reviewed / Open Access
• [Presentation] 本邦のバレット食道及び食道腺癌における欧米との遺伝学的類似・相違点 (2021)
  • Author(s): 徳長鎮, 沖元謙一郎, 加藤直也
  • Organizer: JDDW2021
• [Presentation] 本邦におけるSSBEの発癌ポテンシャルに対する遺伝学的検討(LSBE, EACとの比較)uate risk factors of carcinogenesis? (2021)
  • Author(s): ①徳長鎮,②沖元謙一郎,③加藤直也
  • Organizer: 内視鏡学会2021
• [Presentation] Does the the western Barrett's esophageal diagnostic definition correctly evaluate risk factors of carcinogenesis? (2019)
  • Author(s): Kentaro Ishikawa, Tomoaki Matsumura, Kenichiro Okimoto, Yushi Imai, Tsubasa Oike, Yuya Yokoyama, Naoki Akizue, Yuki Ohta, Takashi Taida, Keiko Saito, Daisuke Maruoka, Tomoo Nakagawa, Makoto Arai, Naoya Kato
  • Organizer: 第27回 消化器関連週間
• [Presentation] COMPREHENSIVE ANALYSIS OF PALISADE VESSELS IN BARRETT'S ESOPHAGUS (2019)
  • Author(s): Kentaro IshikawaTomoaki MatsumuraKenichiro Okimoto et al
  • Organizer: Disestive Disease week 2019 San diego
  • Int'l Joint Research