RRC ID 56118
Author Nakagawa S, Okabe H, Ouchi M, Tokunaga R, Umezaki N, Higashi T, Kaida T, Arima K, Kitano Y, Kuroki H, Mima K, Nitta H, Imai K, Hashimoto D, Yamashita YI, Chikamoto A, Baba H.
Title Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma.
Journal HPB (Oxford)
Abstract BACKGROUND:Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulates tumor malignancy by gene silencing via histone methylation. In this study we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC).
METHODS:The influence of EZH2 on tumor angiogenesis was examined by bioinformatics analysis of a public database. We also assessed the correlation between EZH2 and vasohibin 1 (VASH1) expression in 47 patients with ICC by immunohistochemical (IHC) staining and in vitro gene silencing assays. The prognostic significance of EZH2 and VASH1 expression by IHC was also examined in the ICC cohort.
RESULTS:Bioinformatics analysis showed that EZH2 was associated with several angiogenesis gene sets in the public database. EZH2 suppressed VASH1 expression in in vitro assays and IHC studies. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P = 0.019) and poor overall survival (P = 0.0055).
CONCLUSION:The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC.
Volume 20(10)
Pages 939-948
Published 2018-10-1
DOI 10.1016/j.hpb.2018.03.018
PII S1365-182X(18)30795-0
PMID 29759640
MeSH Bile Duct Neoplasms / genetics Bile Duct Neoplasms / metabolism* Bile Duct Neoplasms / pathology Bile Duct Neoplasms / surgery Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line, Tumor Chemotherapy, Adjuvant Cholangiocarcinoma / genetics Cholangiocarcinoma / metabolism* Cholangiocarcinoma / pathology Cholangiocarcinoma / surgery Disease Progression Disease-Free Survival Enhancer of Zeste Homolog 2 Protein / genetics Enhancer of Zeste Homolog 2 Protein / metabolism* Gene Expression Regulation, Neoplastic Hepatectomy Humans Neoplasm Recurrence, Local* Neovascularization, Pathologic* Predictive Value of Tests Risk Assessment Risk Factors Signal Transduction Time Factors
IF 3.047
Times Cited 3
Human and Animal Cells RBE(RCB1292)