Drug screening for cholangiocarcinoma targeting the epigenetical mechanism of cancer progression

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10191
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: CHIKAMOTO Akira 熊本大学, 医学部附属病院, 准教授 (10419640)
• Co-Investigator(Kenkyū-buntansha): 美馬 浩介 熊本大学, 医学部附属病院, 非常勤診療医師 (00546559) ; 中川 茂樹 熊本大学, 医学部附属病院, 医員 (10594872) ; 岡部 弘尚 熊本大学, 医学部附属病院, 助教 (40573621) ; 林 洋光 熊本大学, 医学部附属病院, 非常勤診療医師 (80625773)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 肝内胆管癌 / EZH2 / VASH1 / 血管新生 / 細胞増殖 / Notch1

Outline of Final Research Achievements

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulate tumor malignancy by gene silencing via histone methylation. In this study, we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC). The influence of EZH2 on tumor angiogenesis and the prognostic significance of EZH2 and VASH1 expression was also examined in ICC cohort by IHC.
By bioinformatical analysis, EZH2 was associated with several angiogenesis gene set in public database. We also find that EZH2 suppress VASH1 expression in vitro assay and IHC study. In IHC analysis. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P=0.019) and poor overall survival (P=0.0055). The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and the EZH2 mediated angiogenesis pathway predicts the prognosis of patients with ICC.

Free Research Field

消化器外科、肝胆膵外科