EYA4 gene functions as a prognosticmarker and inhibits the growth of intrahepaticcholangiocarcinoma

• Published in: 癌症：英文版 2016, Vol.35 (8), p.421-429
• Main Author: Xiao-YiHao Jian-PengCai XinLiu WeiChen XunHou DongChen Jia-ming LaiLi-jianLiang Xiao-YuYin
• Format: Article
• Language: English
• ISSN: 1000-467X; 1944-446X

not been well documented. The purpose of this study was to investigate the prognostic value of the eyes absenthomolog 4 （EYA4） gene in ICC and its biological effects on ICC growth in vitro and in vivo.Methods： One hundred twelve patients with ICC who underwent hepatectomy were enrolled in the study. ￡说4mRNA and EYA4 protein levels in ICC and adjacent non-tumoral tissues were evaluated using real-time quantitativepolymerase chain reaction and immunohistochemical staining, respectively. EYA4 protein levels in ICC cells weredetermined using western blot analysis. The associations between EYA4 expression and clinicopathologic features ofICC were analyzed. To identify independent prognostic factors, univariate and multivariate analyses were performed.The biological effects of EYA4 on ICC cells were evaluated by establishing stable EYA4-overexpressing transfectantsin vitro, and EYA4＇s effects on tumor growth were evaluated by intra-tumoral injection of EYA4-expressing plasmids ina NOD/SCID murine model of xenograft tumors.Results： ICC tissues had significantly lower EYA4 mRNA and protein levels compared with adjacent non-tumoral tissues（both P 〈 0.001）. Univariate and multivariate analyses showed that EYA4 protein level, tumor number, adjacentorgan invasion, lymph node metastasis, and tumor differentiation were independent prognostic factors for diseasefreesurvival and overall survival （all P 〈 0.05）. In vitro, EYA4 overexpression inhibited tumor cell growth, foci formation,and cell invasiveness. In vivo, intra-tumoral injection of ￡KA4-expressing plasmids significantly inhibited ICC growth inthe murine xenograft model compared with the control group （P 〈 0.05）.Conclusion： EYA4 gene functioned as a molecular prognostic marker in ICC, and its overexpression inhibited tumorgrowth in vitro and in vivo.