title: 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.
authors: Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors: Nariyasu
authors: N
authors: Nakashima
authors: Dage
authors: D
authors: Liu
authors: Cheng-Long
authors: CL
authors: Huang
authors: Masaki
authors: M
authors: Ueno
authors: Xia
authors: X
authors: Zhang
authors: Hiroyasu
authors: H
authors: Yokomise
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020598:Proto-Oncogene Proteins c-myb / Q000096:biosynthesis / Q000235:genetics; D000077022:Survivin; D060508:Wnt3 Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D020598:Proto-Oncogene Proteins c-myb; D000077022:Survivin; C555507:WNT3 protein, human; D060508:Wnt3 Protein