J Breast Cancer.  2025 Apr;28(2):86-98. 10.4048/jbc.2024.0224.

Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer

• Lee F
• Cheng SP
• Chen MJ
• Huang WC
• Liu YM
• Chang SC
• Chang YC

• KMID: 2568079
• DOI: http://doi.org/10.4048/jbc.2024.0224

Abstract

Purpose
Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement 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 using tissue microarrays. Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.
Results
Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20.
Conclusion
Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Keyword

Breast Neoplasms; Immunohistochemistry; Recurrence; Tissue Array Analysis