Elucidation of clinical significance and chemotherapy resistance mechanism of NAD(P)H:quinone oxidoreductase 1 (NQO1) expression for colorectal liver metastasis

• Project/Area Number: 17K10663
• 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: Nakano Mae 新潟大学, 医歯学総合病院, 特任助教 (20790281)
• Co-Investigator(Kenkyū-buntansha): 亀山 仁史 新潟大学, 医歯学総合研究科, 客員研究員 (40626420) ; 松田 康伸 新潟大学, 医歯学系, 准教授 (40334669) ; 坂田 純 新潟大学, 医歯学系, 講師 (70447605) ; 小林 隆 新潟大学, 医歯学系, 准教授 (40464010) ; 若井 俊文 新潟大学, 医歯学系, 教授 (50372470)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸癌肝転移 / NQO1 / 薬剤抵抗性 / 薬物療法抵抗性 / 肝臓外科学 / 薬物療法効果予測

Outline of Final Research Achievements

NQO1 is an antioxidant stress protein. The expression of NQO1 is enhanced under stressed environment in vivo. We studied how NQO1 expression affects response of preoperative chemotherapy and prognosis in colorectal liver metastasis. In this study, immunohistochemistry using monoclonal antibody was performed on the resected specimen of colorectal liver metastasis, and the expression of NQO1 was analyzed. The NQO1 positive group had worse overall survival than the NQO1 negative group, and the presence of NQO1 polymorphism was associated with a better response to preoperative chemotherapy. The expression pattern of NQO1 can predict the prognosis and the response of preoperative chemotherapy in patients with colorectal liver metastasis.

Academic Significance and Societal Importance of the Research Achievements

大腸癌の既存のバイオマーカーであるRAS/BRAF変異に加え、大腸癌のNQO1発現や遺伝子多型を評価することにより、大腸癌肝転移に対する術前化学療法の効果予測が可能となり、薬物療法効果予測を基盤とした新しい治療戦略が構築できうると言える。

Research Products

• [Presentation] NQO1 Expression Predicts OS and Response to Preoperative Chemotherapy in Colorectal Liver Metastasis (2019)
  • Author(s): 廣瀬雄己、坂田純、小林隆、滝沢一泰、三浦宏平、堅田朋大、永橋昌幸、島田能史、市川寛、亀山仁史、若井俊文
  • Organizer: 14th ANNUAL ACADEMIC SURGICAL CONGRESS
  • Int'l Joint Research
• [Presentation] 大腸癌肝転移に対する術前化学療法 NQO1発現を用いた治療効果予測の可能性 (2018)
  • Author(s): 相馬大輝、坂田純、小林隆、滝沢一泰、三浦宏平、堅田朋大、石川博補、廣瀬雄己、峠弘治、油座築、安藤拓也、田島陽介、市川寛、羽入隆晃、永橋昌幸、中島真人、島田能史、亀山仁史、若井俊文
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 大腸癌肝転移におけるNQO1発現が肝切除術後の遠隔成績に与える影響 (2018)
  • Author(s): 廣瀬雄己、坂田純、安藤拓也、油座築、峠弘治、堅田朋大、三浦宏平、滝沢一泰、小林隆、永橋昌幸、島田能史、亀山仁史、若井俊文
  • Organizer: 第26回日本消化器関連週間（第17回日本消化器外科学会大会）