Identification of molecular targets to predict postoperative outcomes in patients with neuroendocrine cell carcinoma of the esophagus

• Project/Area Number: 15K10089
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Toyama
• Principal Investigator: Kojima Hirohumi 富山大学, 大学院医学薬学研究部(医学), 助教 (60750114)
• Co-Investigator(Kenkyū-buntansha): 奥村 知之 富山大学, 附属病院, 講師 (10533523)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: NEC / esophagus / Esophageal cancer / miRNA / 神経内分泌癌 / 食道癌 / マイクロRNA / マイクロアレイ / 治療効果予測 / 食道原発小細胞癌

Outline of Final Research Achievements

Background: Neuroendocrine cell carcinoma of the esophagus (ENEC) is a rare but very aggressive disease with poor prognosis. The aim of this study was to identify a molecular signature to predict postoperative outcomes in patients with ENEC. Methods: Expression of microRNA was detected in surgically-removed ENEC tumors using microarrays. A SCCE cell line (TYUC-1) was established to investigate the biological role of differentially expressed microRNAs. Results: Hierarchical clustering of microRNA expression revealed two discrete clusters that were identical to the cases with rapid tumor relapse and the cases with long-term survival, respectively. Migration of TYUC-1 was significantly inhibited by downregulation of miR-625. Conclusion: The expression profiles of microRNAs in tumors may represent a novel predictor for postoperative outcomes in patients with ENEC.

Research Products

• [Journal Article] Enhanced cancer stem cell properties of a mitotically quiescent subpopulation of p75NTR-positive cells in esophageal squamous cell carcinoma. (2017)
  • Author(s): Kojima H, Okumura T, Yamaguchi T, Miwa T, Shimada Y, Nagata T.
  • Journal Title: Int J Oncol Volume: 51 Issue: 1 Pages: 49-62
  • DOI: 10.3892/ijo.2017.4001
  • Peer Reviewed
• [Journal Article] Isoform switch of CD44 induces different chemotactic and tumorigenic ability in gallbladder cancer. (2017)
  • Author(s): Miwa T, Nagata T, Kojima H, Sekine S, Okumura T
  • Journal Title: Int J Oncol. Volume: 51 Issue: 3 Pages: 771-780
  • DOI: 10.3892/ijo.2017.4063
  • Peer Reviewed
• [Journal Article] Circulating tumor cells expressing a cancer stem cell marker CD44 as a diagnostic biomarker in patients with gastric cancer. (2017)
  • Author(s): Watanabe T, Okumura T*, Hirano K, Yamaguchi T, Sekine S, Nagata T, Tsukada K.
  • Journal Title: Oncology Letters. Volume: 13 Issue: 1 Pages: 281-288
  • DOI: 10.3892/ol.2016.5432
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Detection of circulating tumor cells by p75NTR expression in patients with esophageal cancer. (2016)
  • Author(s): Yamaguchi T, Okumura T*, Hirano K, Watanabe T, Nagata T, Shimada Y, Tsukada K
  • Journal Title: World Journal of Surgical Oncology Volume: 14 Issue: 1 Pages: 40-47
  • DOI: 10.1186/s12957-016-0793-9
  • NAID: 120005758258
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma. (2016)
  • Author(s): Yamaguchi T, Okumura T, Hirano K, Watanabe T, Nagata T, Shimada Y, Tsukada K.
  • Journal Title: Int J Oncol Volume: 48 Issue: 5 Pages: 1943-1954
  • DOI: 10.3892/ijo.2016.3432
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The expression of microRNA 574-3p as a predictor of postoperative outcome in patients with esophageal squamous cell carcinoma (2016)
  • Author(s): Okumura T, Kojima H, Miwa T, Sekine S, Hashimoto I, Hojo S, Nagata T, Shimada Y
  • Journal Title: World Journal of Surgical Oncology Volume: 14 Issue: 1 Pages: 228-228
  • DOI: 10.1186/s12957-016-0985-3
  • NAID: 120005997654
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA Profiles to Predict Postoperative Prognosis in Patients with Small Cell Carcinoma of the Esophagus. (2015)
  • Author(s): Okumura T, Shimada Y, Omura T, Hirano K, Nagata T, Tsukada K.
  • Journal Title: Anticancer Res Volume: 35 Pages: 719-727
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] p75NTR 発現に基づく食道扁平上皮癌における静止期癌幹細胞の同定 (2017)
  • Author(s): 小島博文，奥村知之，三輪武史，長田拓哉.
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 食道扁平上皮癌における静止期癌幹細胞マーカーCD271を用いた血中循環癌細胞の検出 (2017)
  • Author(s): 奥村知之、小島博文、山口哲司、三輪武史、渡辺徹、関根慎一、橋本伊佐也、吉岡伊作、嶋田裕、長田拓哉、藤井努
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 「JNETS食道原発神経内分泌癌（NEC）プロジェクト」進捗報告 (2017)
  • Author(s): 奥村知之、小島博文、関根慎一、藤井 努、嶋田 裕、小澤壯治、松原久裕、上本伸二、幕内博康、今村正之
  • Organizer: 第5回日本神経内分泌腫瘍研究会学術集会
• [Presentation] 食道原発神経内分泌腫瘍における分子生物学的サブクラスの同定 (2017)
  • Author(s): 奥村知之、小島博文、関根慎一、荒井美栄、馬場逸人、明石尭久、森山亮仁、渋谷和人、橋本伊佐也、北條荘三、吉岡伊作、長田拓哉、廣川慎一郎、藤井 努
  • Organizer: 富山 GEP-NET 懇話会
  • Invited
• [Presentation] p75NTRを用いた食道癌患者の末梢血循環癌細胞の検出 (2016)
  • Author(s): 小島博文， 山口哲司， 奥村知之， 三輪武史， 平野勝久， 渡辺徹， 長田拓哉， 塚田一博
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2016-07-14
• [Presentation] 食道原発神経内分泌癌におけるマイクロRNA発現プロファイルに基づく切除適応症例の選別． (2016)
  • Author(s): 奥村知之，小島博文，三輪武史，河合俊輔，平野勝久，渡辺 徹，森山亮仁，関根慎一，橋本伊佐也，渋谷和人，北條荘三，松井恒志，吉岡伊作，長田拓哉，嶋田 裕，塚田一博．
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2016-07-14
• [Presentation] 食道癌における静止期幹細胞の同定 (2016)
  • Author(s): 小島博文、奥村知之、山口哲司、平野勝久、渡辺徹、三輪武史、長田拓哉、塚田一博
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪
• [Presentation] 食道原発神経内分泌癌（NEC 小細胞癌）におけるマイクロRNA発現プロファイルを用いた分子生物学的サブクラス同定の試み (2015)
  • Author(s): 奥村知之、小島博文、平野勝久、森山亮仁、関根慎一、橋本伊佐也、渋谷和人、北條荘三、松井恒志、吉岡伊作、長田拓哉、嶋田 裕、塚田一博
  • Organizer: 第3回神経内分泌腫瘍研究会
  • Place of Presentation: 仙台
  • Year and Date: 2015-09-12
• [Presentation] MICRORNA PROFILES TO PREDICT POSTOPERATIVE PROGNOSIS IN PATIENTS WITH SMALL CELL CARCINOMA OF THE ESOPHAGUS (2015)
  • Author(s): T. Okumura, Y. Shimada, T. Watanabe, K. Hirano, T. Yamaguchi, S. Sekine, T. Nagata, K. Tsukada
  • Organizer: The 46th World Congress of Surgery
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2015-08-23
  • Int'l Joint Research