The prognostic value of cadherin switch in bladder cancer
The prognostic value of cadherin switch in bladder cancer
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DOI：
10.3892/or_00000741
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发表时间：
2010-04-01
期刊：
影响因子：
4.2
通讯作者：
Szarvas, Tibor
中科院分区：
文献类型：
--
作者：
Jaeger, Tobias;Becker, Markus;Szarvas, Tibor
E-钙粘蛋白表达的缺失和N-钙粘蛋白表达的无效（“钙粘蛋白转换”）被证明是上皮向间质转化（EMT）的特征，这是一种与癌症进展相关的机制。此外，P-cadherin在不同癌症中的预后作用是有争议的。本研究的目的是探讨“钙粘蛋白开关"基因表达水平与膀胱癌预后的关系。采用实时荧光定量PCR技术对181例膀胱癌患者和7例对照者的冷冻组织样本进行分析。采用Kaplan-Meier对数秩检验和考克斯单因素和多因素分析评估E-、N-和P-cadherin基因表达与预后的相关性。考克斯单因素分析显示，E-cadherin基因表达降低和N-cadherin基因表达增加是癌症相关死亡的危险因素（P=0.087，P=0.005）。分别）。14%（13/92）的肌肉浸润性膀胱癌为N-钙粘蛋白阴性。这些患者的预后明显差于那些N-钙粘蛋白阳性的肌肉浸润性肿瘤（P=0.024）。P-cadherin基因表达是影响胃癌特异性生存期和无复发生存期的独立预后因素（P=0.011，P=0.036）。我们观察到的低阶段和高阶段肿瘤之间的特征性“钙粘蛋白转换”以及E-、N-和P-钙粘蛋白的预后意义表明这些标志物在膀胱癌进展中的重要性。N-cadherin阴性肌层浸润性肿瘤患者预后差提示膀胱癌进展中存在一种非N-cadherin依赖的替代方式。
Loss of E-cadherin expression and vain of N-cadherin expression ('cadherin switch') is shown to he characteristic in epithelial to mesenchymal transition (EMT), a mechanism associated with cancer progression. Furthermore the prognostic role of P-cadherin in different cancers is controversial. The aim of this study was to evaluate the prognostic significance of 'cadherin switch' oil the gene expression level in bladder cancer. Frozen tissue samples of 181 bladder cancer patients and 7 control individuals were analyzed by quantitative real-time PCR. Kaplan-Meier log-rank test and COx univariate and multivariate analysis were performed to assess the prognostic relevance of gene expression of E-, N- and P-cadherin. COx univariate analysis revealed that the decrease of E-cadherin and the gain of N-cadherin gene expression are risk factors for cancer-related death (P=0.087, P=0.005. respectively). Fourteen percent (13/92) of muscle-invasive bladder cancers were N-cadherin-negative. These patients had a significantly poorer prognosis than those with N-cadherin-positive muscle-invasive tumors (P=0.024). P-cadherin gene expression proved to he a significant independent prognostic factor for both cancer-specific and recurrence-free Survival (P=0.011, P=0.036). The characteristic 'cadherin switch' between low- and high-stage tumors that we observed and the prognostic significance of E-, N- and P-cadherin suggests the importance of these markers in bladder cancer progression. The poor patient prognosis in N-cadherin-negative muscle-invasive tumors indicates an alternative, N-cadherin-independent way in bladder cancer progression.