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

Abstract

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.