Qu Yan, Zhang Lin, Wang Jianbo, Chen Pengxiang, Jia Yibin, Wang Cong, Yang Wenjing, Wen Zhihua, Song Qingxu, Tan Bingxu, Cheng Yufeng
Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Exp Ther Med. 2019 Oct;18(4):2993-3001. doi: 10.3892/etm.2019.7896. Epub 2019 Aug 14.
The impact of yes-associated protein (YAP) on the prognosis of patients with esophageal squamous cell cancer (ESCC) and its mechanism of action has seldom been reported. In the present study, the role of YAP on the prognosis of patients with ESCC and the mechanism of action of YAP in promoting the progression of ESCC was investigated. Tumor tissue samples from patients with ESCC were collected and the level of YAP expression was detected using immunohistochemical staining. In addition, YAP was knocked-down in ESCC cell lines and the effects on cell migration and invasion were examined. The expression levels of vimentin, N-cadherin, and E-cadherin were further investigated to examine the association between YAP and epithelial-mesenchymal transition (EMT). Results showed that overexpression of YAP was associated with larger lymph node metastasis and poor disease-free survival and overall survival. Compared with patients in early stage ESCC, the association was more significant in patients with late stage ESCC. Univariate and multivariate analyses further indicated that YAP expression could be an independent prognostic factor for ESCC. Downregulation of YAP inhibited cell migration and invasion. Western blot analysis showed that when YAP was knocked down, expression levels of vimentin and N-cadherin were reduced, whereas that of E-cadherin was increased. In conclusion, the results indicates that YAP expression level could be a novel marker for predicting the prognosis of patients with ESCC, and YAP-promoted tumor migration and invasion might be through EMT in ESCC.
Yes相关蛋白(YAP)对食管鳞状细胞癌(ESCC)患者预后的影响及其作用机制鲜有报道。在本研究中,我们探究了YAP在ESCC患者预后中的作用以及YAP促进ESCC进展的作用机制。收集ESCC患者的肿瘤组织样本,采用免疫组织化学染色检测YAP表达水平。此外,在ESCC细胞系中敲低YAP,并检测其对细胞迁移和侵袭的影响。进一步研究波形蛋白、N-钙黏蛋白和E-钙黏蛋白的表达水平,以探讨YAP与上皮-间质转化(EMT)之间的关系。结果显示,YAP的过表达与更大的淋巴结转移以及较差的无病生存期和总生存期相关。与早期ESCC患者相比,晚期ESCC患者的这种关联更为显著。单因素和多因素分析进一步表明,YAP表达可能是ESCC的一个独立预后因素。YAP的下调抑制了细胞迁移和侵袭。蛋白质印迹分析表明,敲低YAP时,波形蛋白和N-钙黏蛋白的表达水平降低,而E-钙黏蛋白的表达水平升高。总之,结果表明YAP表达水平可能是预测ESCC患者预后的一个新标志物,并且YAP促进肿瘤迁移和侵袭可能是通过ESCC中的EMT实现的。