The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status
The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status
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DOI：
10.1016/j.urolonc.2007.12.012
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发表时间：
2009-05-01
影响因子：
2.7
通讯作者：
Wallerand, Herve
中科院分区：
文献类型：
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作者：
Fondrevelle, Marie E.;Kantelip, Bernadette;Wallerand, Herve
目的：TWIST被认为是一种转录因子，至少通过抑制E-钙粘蛋白的表达来调节上皮间质转化(EMT)。EMT是肿瘤侵袭过程中的关键事件。本研究的目的是探讨Twist、E-钙粘蛋白和N-钙粘蛋白在人原发膀胱肿瘤中的表达及其预后价值。由于吸烟是膀胱癌的重要危险因素，我们试图评估吸烟状况对这些分子异常的影响。材料和方法：为了阐明Twist在人膀胱癌中的致癌作用，我们用免疫组织化学方法检测了E-和N-钙粘蛋白以及Twist的表达(n=70)。我们评估了这些表达的预后价值。此外，我们试图将这些蛋白的表达与患者的吸烟状况联系起来。结果：70例膀胱肿瘤中，Twist阳性表达28例(40%)，E-cadherin阴性16例(23%)，N-cadherin阳性12例(17%)。TWIST与临床分期(P=0.001)、分级(P=0.001)、进展期(P=0.02)、E-钙粘素表达(P=0.001)相关。此外，Twist阳性表达明显预示PFS较差(P=0.02)。在多因素分析中，TWIST阳性表达和E-钙粘蛋白表达缺失均是PFS的独立预后因素(P=0.046和P=0.001)，而仅E-钙粘素表达缺失是OS的独立预后因素(P<；0.001)。我们还证明了近60%(16/28)Twist阳性表达的患者在确诊时是当前吸烟者，这证实了吸烟调节包括Twist在内的EMT标志物表达的事实。结论：Twist阳性表达可能是膀胱癌患者有用的预后标志物。它的表达似乎与患者的吸烟状况有关。(C)2009 Elsevier Inc.保留所有权利。
Objectives: Twist is considered as transcription factor that regulates epithelial mesenchymal transition (EMT) by at least inhibition of E-cadherin expression. EMT is a key event in the tumor invasion process. The purpose of this study is to investigate the expression of Twist but also those of E- and N-cadherin in human primary bladder tumor and to evaluate its prognostic value. As smoking cigarettes is a strong bladder cancer risk factor, we tried to evaluate the impact of the tobacco status on these molecular abnormalities.Materials and Methods: To delineate on the oncogenic role for Twist in human bladder cancer, we evaluated the E- and N-cadherin but also Twist expression (n = 70) by immunohistochemistry. We evaluated the prognostic value of these expressions. Moreover, we tried to correlate these protein expressions to the smoking status of the patients. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis.Results: Of the 70 bladder tumors, 28 (40%) cases were positive for Twist expression, 16 (23%) cases were negative for E-cadherin expression, and 12 (17%) were positive for N-cadherin expression. When categorized into negative vs. positive expression, Twist was associated with the stage (P = 0.001), the grade (P < 0.001), the progression (P = 0.02), and the E-cadherin expression (P = 0.01). Moreover, positive Twist expression clearly predicted poorer PFS (P = 0.02). In the multivariate analysis, both positive Twist expression and loss of E-cadherin expression were independent prognostic factors for PFS (P = 0.046 and P = 0.001, respectively) and only loss of E-cadherin expression for the OS (P < 0.001). We also demonstrated that almost 60% (16/28) of patients with Twist-positive expression were current smokers at the time of the diagnosis, corroborating the fact that smoking modulates the expression of EMT markers including Twist.Conclusion: Positive Twist expression may be a useful prognostic marker for patients with bladder cancer. Its expression seems to be correlated to the tobacco status of the patients. (C) 2009 Elsevier Inc. All rights reserved.