Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
PLoS One. 2013 May 2;8(5):e62558. doi: 10.1371/journal.pone.0062558. Print 2013.
ZEB2 has been reportedly shown to mediate the epithelial-to-mesenchymal transition (EMT) and disease aggressiveness in human tumors. However, the expression status of ZEB2 in renal cell carcinoma (RCC) and ZEB2's clinicopathologic/prognostic significance are poorly understood.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, tissue microarray, immunohistochemistry (IHC) and western blot analyses were utilized to investigate the ZEB2 expression status in RCC and adjacent renal tissue samples. In our study, samples from 116 RCC patients treated with radical nephrectomy were used as a training set to generate a ZEB2 optimal cut-point for patient outcome by receiver operating characteristic (ROC) analysis. For validation, the correlation of ZEB2 expression with the clinical characteristics and patient outcomes in another set (including 113 patients) was analyzed to validate the obtained cut-point. In the training and validation sets, high expression of ZEB2, defined by ROC analysis, predicted a poorer overall survival and progression-free survival, as evidenced by the univariate and multivariate analyses. In different subsets of overall patients, ZEB2 expression was also a prognostic indicator in patients with stage I/II, stage III/IV, grade 1/2 and grade 3/4 disease (P<0.05). Downregulation of ZEB2 by shRNA decreased the migration and invasion ability of 769-P cells in vitro. Furthermore, high ZEB2 expression was positively correlated with vimentin expression and inversely linked to E-cadherin expression in RCC.
CONCLUSIONS/SIGNIFICANCE: Our findings provide a basis for the concept that high ZEB2 expression in RCC may be important in the acquisition of an aggressive phenotype. This evidence suggests that ZEB2 overexpression (examined by IHC) is an independent biomarker for the poor prognosis of patients with RCC.
据报道，ZEB2 介导了人类肿瘤的上皮间质转化（EMT）和疾病侵袭性。然而，ZEB2 在肾细胞癌（RCC）中的表达状态以及 ZEB2 的临床病理/预后意义尚不清楚。
方法/主要发现：本研究利用组织微阵列、免疫组织化学（IHC）和 Western blot 分析检测了 RCC 及相邻肾组织样本中 ZEB2 的表达状态。在本研究中，采用根治性肾切除术治疗的 116 例 RCC 患者的样本作为训练集，通过接受者操作特征（ROC）分析生成 ZEB2 用于预测患者预后的最佳截断值。为了验证，通过分析 ZEB2 表达与另一个包含 113 例患者的队列中患者的临床特征和结局的相关性来验证获得的截断值。在训练和验证队列中，通过单变量和多变量分析，通过 ROC 分析定义的 ZEB2 高表达预示着总生存期和无进展生存期较差。在所有患者的不同亚组中，ZEB2 表达也是 I 期/II 期、III 期/IV 期、1/2 级和 3/4 级疾病患者的预后指标（P<0.05）。shRNA 下调 ZEB2 的表达降低了 769-P 细胞的迁移和侵袭能力。此外，在 RCC 中，ZEB2 高表达与波形蛋白表达呈正相关，与 E-钙黏蛋白表达呈负相关。
结论/意义：我们的研究结果为 ZEB2 在 RCC 中的高表达可能在获得侵袭性表型方面具有重要作用的概念提供了依据。这些证据表明，ZEB2 过表达（通过 IHC 检测）是 RCC 患者预后不良的独立生物标志物。
