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

2019 Fiscal Year Final Research Report

• 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
• Keywords: 大腸癌肝転移 / NQO1 / 薬剤抵抗性

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.

Free Research Field

消化器外科学

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。