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Wnt5a Expression Is Associated With the Tumor Proliferation and the Stromal Vascular Endothelial Growth Factor—An Expression in Non–Small-Cell Lung Cancer

From the Departments of Second Surgery and Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan

Address reprint requests to Cheng-long Huang, MD, Department of Second Surgery, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; e-mail: chuang{at}kms.ac.jp

PURPOSE: The Wnt 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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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