Snail Expression Is Associated With a Poor Prognosis in Malignant Pleural Mesotheliomas
Snail Expression Is Associated With a Poor Prognosis in Malignant Pleural Mesotheliomas
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DOI：
10.1016/j.athoracsur.2013.01.012
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发表时间：
2013-04-01
影响因子：
4.6
通讯作者：
Date, Hiroshi
中科院分区：
文献类型：
--
作者：
Kobayashi, Masashi;Huang, Cheng-long;Date, Hiroshi
背景恶性胸膜间皮瘤（MPM）是一种预后不良的侵袭性肿瘤。我们的目的是通过分析上皮间质转化（EMT）相关转录因子和E-cadherin的表达与肿瘤增殖率和患者生存率的关系来阐明MPM中EMT的机制。研究了109例MPM患者。其中上皮样肿瘤61例，肉瘤样肿瘤21例，双相肿瘤20例，促结缔组织增生性肿瘤7例。免疫组化检测Snail、ZEB 1、Twist、E-cadherin的表达及Ki-67增殖指数。Snail和ZEB 1在非上皮样肿瘤中的表达明显高于上皮样肿瘤（分别为p < 0.0001和p = 0.0051）。此外，E-钙粘蛋白的表达显着低于蜗牛高肿瘤比蜗牛低肿瘤（p = 0.0423）。非上皮样肿瘤的E-钙粘蛋白表达显著低于上皮样肿瘤（p = 0.0126）。Ki-67增殖指数在非上皮样肿瘤中显著高于上皮样肿瘤（p = 0.025）。Snail高MPM患者的生存率显著低于Snail低MPM患者（p = 0.0016），尤其是非上皮样肿瘤患者（p = 0.0089）。多因素分析还表明，核Snail表达是MPM患者预后不良的重要预测因素（p = 0.0142）。Snail表达与MPM中的EMT和不良预后相关。Snail可能成为治疗MPM的潜在分子靶点。(Ann Thorac Surg 2013;95：1181-8）（C）2013，胸外科医师协会
Background. Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival.Methods. One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index.Results. The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p < 0.0001 and p = 0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p = 0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p = 0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p = 0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p = 0.0016), especially in patients with nonepithelioid tumors (p = 0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p = 0.0142).Conclusions. The Snail expression is associated with EMT and a poor prognosis in MPMs. Snail could be a potential molecular target for the treatment of patients with MPMs. (Ann Thorac Surg 2013;95:1181-8) (C) 2013 by The Society of Thoracic Surgeons