The relationship of microRNA expression on the signaling pathway activation in pancreatic intraductal papillary mucinous neoplasm

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08696
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Juntendo University
• Principal Investigator: Fukumura Yuki 順天堂大学, 医学部, 准教授 (90407312)
• Co-Investigator(Kenkyū-buntansha): 三富 弘之 順天堂大学, 医学部, 非常勤講師 (90181940)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 膵管内乳頭粘液性腫瘍 / miR21 / miR181b / miR20-a / シグナル伝達経路 / Wnt/β-catenin / Akt/mTOR

Outline of Final Research Achievements

Malignant transformation/stromal invasion of pancreatic intraductal papillary mucinous neoplasm (IPMN) requires the activation of Wnt/β-catenin, GTP-binding protein related, AKT/mTOR, Hedgehog signal pathways. This study analyzed microRNAs which associates with these signal pathway activation in IPMN.
By quantification of miRs in resected IPMN specimen, high expression of miR 21 was seen in carcinoma in situ and invasive IPMN; high expression of miR181b was seen in invasive IPMN; and high expression of miR20-a tended to relate with invasive IPMN. By Nanostring nCounter method, the malignancy/non-malignancy and histological subtype of IPMN were related with activation pattern of the signal pathways.

Free Research Field

胆道・膵臓腫瘍

Academic Significance and Societal Importance of the Research Achievements

膵IPMNは浸潤癌となると生命予後が悪いため、その悪性化の早期段階で発見し、手術する必要がある。本研究で、悪性IPMNにおいてmiR21, miR181bが高値を示すことを発見し、これらは、悪性IPMNの検出のための膵液や血液中バイオマーカーとなりうる可能性を示唆し得た。今後、膵液・血液などを用いた前向き検討を行う必要がある。
これらのmiRとシグナル伝達経路との関連に関しては、手術検体症例数を増やし、組織亜型・悪性度別の解析を行い検討する。また、膵癌株化細胞にmiRのtransfectionを行い、伝達経路への関与を検討する所存である。