Development of liquid biopsy using exosomes released from patient-derived colorectal adenoma organoid

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17421
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tohoku University
• Principal Investigator: Moroi Rintaro 東北大学, 大学病院, 助教 (90803594)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 大腸癌 / 大腸腺腫 / オルガノイド

Outline of Final Research Achievements

We established organoid cultures from normal colon and CRA using resected specimens. Exosomes were isolated from the conditioned medium organoids. To identify candidates miRNAs for liquid biopsy, we prospectively compared changes in their expression in serum and exosomes before and after endoscopic resection in 26 patients with CRA.Seven exosomal miRNAs were overexpressed in CRA organoids: miR-4323, miR-4284, miR-1268a, miR-1290, miR-6766-3p, miR-21-5p, and miR-1246.The expression levels of four exosomal miRNAs (miR-4323, miR-4284, miR-1290, and miR-1246) and two serum miRNAs (miR-1290 and miR-1246) were significantly lower in post-treatment sera. Combined expression of four exosomal miRNAs could identify both CRA with respective areas under the curve (AUCs) of 0.698. We found that exosomal miRNAs derived from CRA organoid culture could be potential diagnostic biomarkers for CRA.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

本研究ではオルガノイド培養技術を用いることでこれまで困難であった大腸腺腫のエクソソームの評価とリキッドバイオプシーの有用性を明らかにした。オルガノイド培養技術を用いることで、臓器、疾患を問わずエクソソーム研究が可能となる。今後疾患特異的なエクソソームを明らかにすることで機能解析や新たなバイオマーカーの発見、さらにはそれらをターゲットとした治療にも繋がると考えられる。また、本研究で明らかにしたバイオマーカーを用いることで、これまでのスクリーニング検査で発見困難であった大きな大腸腺腫を発見できる可能性がある。