Wnt3 gene expression promotes tumor progression in non-small cell lung cancer

The Wnt gene family encodes the multi-functional signaling glycoproteins regulating various normal and pathological processes including tumorigenesis. We investigated the clinical significance of the Wnt3 gene expression in relation to its target genes, c-Myc and survivin, in patients with non-small cell lung cancer (NSCLC). One hundred and twenty-eight patients who underwent resection of NSCLC were analyzed. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of Wnt3, c-Myc, and survivin. Immunohistochemistry was performed to investigate the protein expression of Wnt3, c-Myc, and survivin. The Ki-67 proliferation index and the apoptotic index using the TUNEL method were also evaluated. Twenty-four carcinomas (18.8%) were found to be high-Wnt3 tumors. The high-Wnt3 tumors were significantly more in squamous cell carcinomas than that in adenocarcinomas (P = 0.0022). The Wnt3 gene expression was significantly associated with gene expressions of c-Myc (P = 0.0103) and survivin (P = 0.0009). As a result, the Ki-67 proliferation index was significantly higher in high-Wnt3 tumors than in low-Wnt3 tumors (P = 0.0056). The apoptotic index was significantly lower in high-Wnt3 tumors than in low-Wnt3 tumors (P = 0.0245). The overall survival rate was significantly lower in patients with high-Wnt3 tumors than in those with low-Wnt3 tumors (P = 0.0020). A Cox regression analysis demonstrated that the Wnt3 status was a significant prognostic factor for NSCLC patients (hazard ratio 2.226, P = 0.0296). The present study revealed that Wnt3 gene expression was significantly associated with c-Myc and survivin gene expressions, tumor proliferation, and tumor apoptosis. During the progression of NSCLC, Wnt3 overexpression could be associated with the development of more aggressive tumors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.