Detection of Circulating MicroRNAs with Ago2 Complexes to Monitor the Tumor Dynamics of Colorectal Liver Metastasis Patients during Chemotherapy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: Umeda Yuzo 岡山大学, 大学病院, 講師 (10573735)
• Co-Investigator(Kenkyū-buntansha): 藤原 俊義 岡山大学, 医歯薬学総合研究科, 教授 (00304303) ; 八木 孝仁 岡山大学, 大学病院, 教授 (00304353) ; 永坂 岳司 川崎医科大学, 医学部, 准教授 (30452569)
• Research Collaborator: FUJI Tomokazu ; MORI Yoshiko ; YASUI Kazuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Precision medicine / 大腸癌肝転移 / Liquid Biopsy / マイクロRNA

Outline of Final Research Achievements

We examined Two different forms of circulating miRNAs in plasma: Argonaute2 (Ago2)-miRNAs and extracellular vesicles (EVmiRNAs). Ago2-miR-21 could be released into the extracellular fluid by active export from viable cancer cells and cytolysis in vitro. As miR-21 and miR-200c were expressed in both liver metastasis and primary lesions, we evaluated Ago2-miR-21 as a candidate biomarker of both active export and cytolysis while Ago2-miR-200c as a biomarker of cytolysis in a series of plasma obtained from colorectal cancer (CRC) patients with liver metastasis who received systemic chemotherapy. Ago2-miR-21 allowed us to distinguish CRC from subjects without CRC. The trend in ΔCt values for Ago2-miR-21 and miR-200c during chemotherapy could predict tumor response to ongoing treatment. Thus, capturing circulating Ago2-miRNAs from active export can screen patients with tumor burdens, while capturing them from passive release by cytolysis can monitor tumor dynamics during chemotherapy.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究により、循環Ago2-miRNAを対象としたLiquid Biopsyによる非侵襲的かつ簡便に遺伝子変異情報を把握する新しい臨床検査法が確立され、癌スクリーニングや進行癌におけるダイナミックな腫瘍病勢のモニタリングが可能となった。
本研究手法によって、精緻な個別化医療が叶えば、今後の本邦の大腸癌治療成績を飛躍的に発展させるだけでなく、無用な補助療法を回避する等、患者側面のみならず診療費削減といったCost benefitにも十分に寄与し得る。また同手法は、他の肝癌に対する肝移植や他の消化器悪性疾患の外科治療にも応用できる可能性があり、本臨床医学研究の意義は極めて深いと考えられる。