Development of a new molecular diagnostic method and molecular targeted therapies for pancreatic ductal adenocarcinomas using RHO pathway-regulating proteins

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08684
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hokkaido University
• Principal Investigator: Mitsuhashi Tomoko 北海道大学, 大学病院, 准教授 (60348208)
• Co-Investigator(Kenkyū-buntansha): 畑中 豊 北海道大学, 大学病院, 特任准教授 (30589924)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 浸潤性膵管癌 / RHO経路 / 治療効果予測

Outline of Final Research Achievements

In this study, basic experiments were performed for the development of a new molecular diagnostic method and molecular targeted therapies for pancreatic ductal adenocarcinomas (PDACs), by focusing on multiple RHO pathway-regulating (RPR) proteins identified in our preceding studies. Gene expression profiling (GEP) data of RPR proteins was analyzed using public microarray data of PDAC cell lines. Twenty-one PDAC cell lines were divided into 3 clusters (Cluster 1 to 3), of which, Clusters 3 and 2 corresponded to QM and CL subtype of PDAC, respectively, as previously reported by Collison et al. Furthermore, the results of GEP data of EUS-FNA biopsies were also similar to those from PDAC cell lines. Thus, the molecular subtypes, reflecting the molecular pathophysiology and effectiveness of chemotherapy, could be associated with PRP gene expression profiles. Furthermore, results of this study can aid the development of molecular diagnostic methods and molecular targeted therapies for PDAC.

Free Research Field

人体病理

Academic Significance and Societal Importance of the Research Achievements

本研究により，Collisonらの提唱する膵癌の分子サブタイプと複数のRHO経路制御（RPR）分子（ARHGAP/ARHGEF）遺伝子発現プロファイルが関係することが示唆され，予後不良な膵癌の個別化治療に応用しうる膵癌分子診断法の開発に繋がる可能性を有する．RHO経路に関わる分子の遺伝子発現シグネチャーに着目した研究はこれまでにないことから，学術的意義が大きいといえる．またこの経路を阻害する薬剤はすでに開発されていることから，標的治療法の開発に繋がる可能性も有する．