Analysis of driver gene mutation using organoid model

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07016
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Hiroshima University
• Principal Investigator: Oue Naohide 広島大学, 医系科学研究科(医), 准教授 (60346484)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胃癌 / 幹細胞 / 大腸癌

Outline of Final Research Achievements

Spheroid colony formation is a useful method of cancer stem cell characterization. We found that QPRT、CST2、ANKRD45、ZWINT、FAM111B gene is up-regulated in spheroid body-forming cancer cells compared with parental cells. We investigated ZWINT expression in colorectal cancer. Immunohistochemical analysis demonstrated that 61 (47%) of 129 colorectal cancer cases were positive for ZWINT and ZWINT expression was significantly correlated with KIFC1 expression. ZWINT-positive cases exhibited significantly worse overall survival. KIFC1 siRNA-transfected cells showed reduced ZWINT expression while ZWINT siRNA-transfected cells decreased cell proliferation. Both KIFC1 and ZWINT knockdown cells attenuated spheroid formation ability. This study provides new insights into KIFC1 regulating ZWINT in colorectal cancer progression and its potential as a therapeutic target.

Free Research Field

分子病理学

Academic Significance and Societal Importance of the Research Achievements

ZWINTは47%の大腸癌で高発現しおり、高発現例は有意に予後不良であったことから、大腸癌の予後予測マーカーとして有用である。さらにZWINTは癌幹細胞のマーカーであるKIFC1陽性細胞において発現していたことから、幹細胞において重要な役割を果たしている可能性もあり、治療標的としても期待される。