Elucidation of the mechanism of drug resistance in colorectal cancer by p62-Keap 1-Nrf2 pathway

• Project/Area Number: 26462006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Niigata University
• Principal Investigator: KAMEYAMA Hitoshi 新潟大学, 医歯学系, 准教授 (40626420)
• Co-Investigator(Kenkyū-buntansha): 若井 俊文 新潟大学, 医歯学系, 教授 (50372470) ; 味岡 洋一 新潟大学, 医歯学系, 教授 (80222610) ; 西條 康夫 新潟大学, 医歯学系, 教授 (10270828) ; 松田 康伸 新潟大学, 医歯学系, 准教授 (40334669) ; 小山 諭 新潟大学, 医歯学系, 教授 (10323966) ; 廣瀬 雄己 新潟大学, 医歯学総合病院, 医員 (10737365) ; 小杉 伸一 新潟大学, 医歯学総合病院, 特任教授 (90401736) ; 小林 隆 新潟大学, 医歯学総合病院, 講師 (40464010) ; 永橋 昌幸 新潟大学, 医歯学総合病院, 講師 (30743918)
• Co-Investigator(Renkei-kenkyūsha): KOMATSU Masaaki 新潟大学, 医歯学系, 教授 (90356254)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 大腸癌 / 抗癌剤耐性 / NQO1 / KRAS / Nrf2 / Keap1 / p62

Outline of Final Research Achievements

p62-Keap1-Nrf2 pathway induce the antioxidants like NQO1. In cancer cells, NQO1 confers resistance against anticancer agents. The aim of this study was to evaluate the association between NQO1 expression and prognosis in patients with advanced colorectal cancer (CRC). Among the patients with KRAS wild CRC, NQO1-negative patients showed significantly better disease control rate than NQO1-positive patients. Moreover, NQO1-negative patients had longer progression-free survival and overall survival than NQO1-positive patients. NQO1 expression in the tumor may be a predictor of therapeutic efficacy and prognosis in patients with KRAS wild advanced CRC.

Research Products

• [Journal Article] Clinical significance of NQO1 expression in patients with advanced KRAS wild colorectal cancer (2017)
  • Author(s): Hitoshi Kameyama, Yuki Hirose, Yasunobu Matsuda, Masayuki Nagahashi, Hiroshi Ichikawa, You Sato, Saki Yamada, Shinnosuke Hotta, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai
  • Journal Title: Int J Clin Exp Pathol Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 切除不能・再発大腸癌における NAD（P）H: quinone oxidoreductase 1発現の臨床的意義 (2015)
  • Author(s): 佐藤 洋
  • Journal Title: 新潟医学会雑誌 Volume: 129 Pages: 300-308
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 大腸癌化学療法におけるNQO1発現解析の意義 (2016)
  • Author(s): 亀山仁史，廣瀬雄己，島田能史，八木亮磨，田島陽介，岡村拓磨，中野雅人，市川 寛，永橋昌幸，坂田 純，小林 隆，若井俊文
  • Organizer: JDDW 2016
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-11-05
• [Presentation] Clinical significance of NQO1 expression in patients with KRAS wild-type unresectable colorectal cancer (2016)
  • Author(s): Hitoshi Kameyama, Yuki Hirose, Yoshifumi Shimada, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Masayuki Nagahashi, Takashi Kobayashi, Toshifumi Wakai
  • Organizer: IASGO 2016
  • Place of Presentation: Seoul (South Korea)
  • Year and Date: 2016-09-10
  • Int'l Joint Research
• [Presentation] NQO1 EXPRESSION HAS PROGNOSTIC SIGNIFICANCE IN KRAS-WILD UNRESECTABLE COLORECTAL CANCER (2015)
  • Author(s): Y. Hirose, H. Kameyama, T. Ohashi, K. Takizawa, M. Nagahashi, T. Kobayashi, J. Sakata, T. Wakai
  • Organizer: 46th World Congress of Surgery
  • Place of Presentation: Bangkok
  • Year and Date: 2015-08-23 – 2015-08-27
• [Presentation] 進行再発大腸癌におけるNQO1発現の臨床的意義 (2014)
  • Author(s): 亀山仁史，廣瀬雄己，佐藤 洋，山田沙季，阿部 馨，庭野稔之，岩城孝和，八木亮磨，田島陽介，中野麻恵，中野雅人，島田能史，坂田 純，小林 隆，皆川昌広，小杉伸一，小山 諭，若井俊文
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-04-16 – 2014-04-18