Wnt5a expression is associated with the tumor proliferation and the stromal vascular endothelial growth factor - An expression in non-small-cell lung cancer
Wnt5a expression is associated with the tumor proliferation and the stromal vascular endothelial growth factor - An expression in non-small-cell lung cancer
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DOI：
10.1200/jco.2005.02.2871
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发表时间：
2005-12-01
影响因子：
45.3
通讯作者：
Ueno, M
中科院分区：
文献类型：
--
作者：
Huang, CL;Liu, D;Ueno, M
目的Writ基因家族编码多功能信号糖蛋白。本研究旨在探讨Wnt 5a在非小细胞肺癌（NSCLC）中的表达及其临床意义。实时定量逆转录聚合酶链反应进行评估Wnt 5a基因的表达。免疫组化检测Wnt 5a蛋白表达、Ki-67增殖指数、肿瘤血管生成、β-catenin和血管内皮生长因子-A（VEGF-A）的表达。标准化Wnt 5a基因表达率与肿瘤内Wnt 5a蛋白表达之间存在显著相关性（r = 0.729; P < .0001）。肿瘤内Wnt 5a表达与Ki-67增殖指数显著相关（r = 0.708; P <0.0001）。相反，在肿瘤内Wnt 5a表达和肿瘤血管生成之间没有观察到相关性。此外，肿瘤内Wnt 5a表达与β-连环蛋白（r = 0.729; P < .0001）和VEGF-A（r = 0.661; P < .0001）的间质表达显著相关。此外，间质VEGF-A表达与Ki-67增殖也相关（r = 0.627; P < .0001）。考克斯回归分析显示Wnt 5a状态是NSCLC患者的一个重要预后因素（P = 0.0193），尤其是鳞状细胞癌患者（P = 0.0491）。
Purpose The Writ gene family encodes the multifunctional signaling glycoproteins. We performed the present study to investigate the clinical significance of Wnt5a expression in non-small-cell lung cancer (NSCLC).Patients and Methods One hundred twenty-three patients with NSCLC who had undergone resection were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction was performed to evaluate the Wnt5a gene expression. Immunohistochemistry was performed to investigate the Wnt5a protein expression, the Ki-67 proliferation index, tumor angiogenesis, and the expression of beta-catenin and vascular endothelial growth factor-A (VEGF-A).Results Wnt5a gene expression in squamous cell carcinoma was significantly higher than that in adenocarcinoma (P < .0001). There was a significant correlation between the normalized Wnt5a gene expression ratio and the intratumoral Wnt5a protein expression (r = 0.729; P < .0001). The intratumoral Wnt5a expression was significantly correlated with the Ki-67 proliferation index (r = 0.708; P < .0001). In contrast, no correlation was observed between the intratumoral Wnt5a expression and tumor angiogenesis. Furthermore, the intratumoral Wnt5a expression was significantly correlated with the stromal expression of beta-catenin (r = 0.729; P < .0001) and VEGF-A (r = 0.661; P < .0001). In addition, the stromal VEGF-A expression was also correlated with Ki-67 proliferation (r = 0.627; P < .0001). Cox regression analyses demonstrated Wnt5a status to be a significant prognostic factor for NSCLC patients (P = .0193), especially for patients with squamous cell carcinomas (P = .0491).Conclusion The present study revealed that an overexpression of Wnt5a could produce more aggressive NSCLC, especially in squamous cell carcinomas, during tumor progression.