Biomarkers in exosome extracted from duodenal fluid for early detection of pancreatobiliary malignancy

Research Project

Project/Area Number	18K08648
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Kyushu University
Principal Investigator	TAKAHATA Shunichi 九州大学, 医学研究院, 共同研究員 (50437779)
Co-Investigator(Kenkyū-buntansha)	大塚隆生九州大学, 医学研究院, 准教授 (20372766) 森泰寿九州大学, 大学病院, 助教 (50632642) 貞苅良彦九州大学, 医学研究院, 共同研究員 (80784503)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	胆道癌 / セネセンス / マイクロRNA / 膵癌 / 十二指腸液 / エクソソーム / exosome
Outline of Final Research Achievements	Compared to other body fluid, pancreatic juice, bile, and duodenal fluid would be better sources of DNA, RNA, proteins, and exosomes derived from neoplastic cells of pancreatobiliary system and have the potential to increase sensitivity/specificity of biomarkers to identify pancreatobiliary cancer. We prospectively collected pancreatic juice, bile, and duodenal fluid from patients with pancreatobiliary malignancy. In our initial study, we extracted exosomal miRNA from pancreatic juice and identified miRNA-21 and miRNA-155 as biomarkers for diagnosis of pancreatic cancer. We also succeeded extraction of exosome from duodenal fluid which have potential to utilize for minimally-invasive screening of pancreatic cancer.
Academic Significance and Societal Importance of the Research Achievements	膵液細胞診は膵癌診断において感度が比較的低く，穿刺吸引細胞診を要することも稀ではない．われわれが開発した膵液中のexosomal RNAからmiRNAの発現解析を組み合わせることで高い正診率を得ることができ，患者に複数回の内視鏡検査を行う負担を軽減することが可能になる．また，十二指腸液中のexosomeの抽出は可能であったため，内包されるmiRNA, DNAの解析で膵癌・胆道癌診断ができれば，健常者の検診でも膵癌・胆道癌のスクリーニングが可能である．罹患率は低いものの，生物学的悪性度が高いために，高い癌関連死亡率を示す膵・胆道癌の早期診断による社会的な貢献度も大きいと考える。