2019 Fiscal Year Final Research Report

Intraperitoineal exosome as a novel target for peritoneal metastasis

Research Project

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Project/Area Number	17H04286
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Digestive surgery
Research Institution	Jichi Medical University
Principal Investigator	KITAYAMA JOJI 自治医科大学, 医学部, 教授 (20251308)
Co-Investigator(Kenkyū-buntansha)	佐田尚宏自治医科大学, 医学部, 教授 (20261977) 山口博紀自治医科大学, 医学部, 教授 (20376445) 三木厚自治医科大学, 医学部, 講師 (20570378) 細谷好則自治医科大学, 医学部, 教授 (30275698) 大澤英之自治医科大学, 医学部, 講師 (60458271) 寺谷工自治医科大学, 医学部, 講師 (70373404)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	エクソソーム / microRNA / 腹膜播種 / 腹腔内化学療法 / バイオマーカー
Outline of Final Research Achievements	Exosomes were isolated from peritoneal fluids of patients of gastric cancer with or without peritoneal metastasis (PM) and comprehensive miRNA expression analysis was performed. In initial screening, we identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis revealed that 4 miRNAs (miR-21-5p, miR-92a-3p, miR-223-3p, and miR-342-3p) were significantly upregulated in 12 PM (+) samples, and their expression levels showed positive correlation with peritoneal cancer index. In contrast, miR-29 family were all downregulated in patients with PM (+) samples. Moreover, miR-29b at gastrectomy was lower in patients with peritoneal recurrence. Ratios of miR-21-5p/miR-29b-3p and miR-223-3p/miR-29b-3p were inversely associated with tumor response and overall survival of the patients who received intraperitoneal chemotherapy. Expression pattern of miRNAs in peritoneal exosome well reflects the tumor burden in peritoneal cavity and could be useful biomarker in the treatment of PM.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	血中エクソソーム成分ががんを含めた様々な病気のバイオマーカーとなることが報告されてきている反面、腹腔内液中のエクソソームの組成に関する情報は乏しかった。本研究で、胃癌患者から採取された腹腔内液中エクソソーム内のマイクロRNAの発現様式が、腹膜播種の病勢を反映し治療に応用できるバイオマーカーとなりうることが判明した。本研究は、その成果が難治性の腹膜播種の治療成績の向上に貢献するとともに、唾液、尿などの体液中に安定するエクソソームの解析が病態の理解や新規治療の開発に向けた糸口となりうることを示した点でも社会的意義があると思われる。