Zinc finger protein 639 expression is a novel prognostic determinant in breast cancer

Background: ZNF639 is often contained within the overlapping amplicon of PIK3CA, and previous studies suggest that it was involved in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed on our tissue microarrays. Functional studies including colony formation, transwell cell migration, and in vivo metastasis were performed in breast tumor cells with ZNF639 knockdown by siRNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of breast cancer samples independent of hormone receptor and HER2 status. In multivariate Cox regression analyses, ZNF639 expression was negatively associated with recurrence-free survival (hazard ratio = 0.36) and marginally with overall survival (hazard ratio = 0.42). ZNF639 knockdown increased clonogenicity, cell motility, and murine lung metastasis. Snail1, vimentin, and CCL20 expression were upregulated following ZNF639 knockdown, and ZNF639-mediated changes in cell phenotype were neutralized by CCL20 double-knockdown. Conclusion: Low ZNF639 expression represents a novel prognostic factor for recurrence-free survival in patients with breast cancer.