Lee Fang, Cheng Shih-Ping, Chen Ming-Jen, Huang Wen-Chien, Liu Yi-Min, Chang Shao-Chiang, Chang Yuan-Ching
Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan.
Department of Medicine, School of Medicine, MacKay Medical College, New Taipei City, Taiwan.
J Breast Cancer. 2025 Apr;28(2):86-98. doi: 10.4048/jbc.2024.0224. Epub 2025 Mar 9.
Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of , 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.
Immunohistochemical analysis of ZNF639 was performed using tissue microarrays. Functional studies, including colony formation, Transwell cell migration, and metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.
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.
Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.
锌指蛋白639（ZNF639）常存在于重叠扩增子中，既往研究提示其参与食管和口腔鳞状细胞癌的发病机制。然而，其在乳腺癌中的表达及意义尚不明确。
利用组织芯片对ZNF639进行免疫组化分析。通过小干扰RNA转染对ZNF639敲低的乳腺肿瘤细胞进行功能研究，包括集落形成、Transwell细胞迁移和转移。
在82%的乳腺癌样本中观察到ZNF639免疫反应性降低，与激素受体和人表皮生长因子受体2状态无关。在多变量Cox回归分析中，ZNF639表达与良好的生存结局相关，包括无复发生存（风险比，0.35；95%置信区间[CI]，0.14 - 0.89）和总生存（风险比，0.41；95% CI，0.16 - 1.05）。ZNF639敲低增加了NOD/SCID小鼠的克隆形成能力、细胞运动性和肺转移。ZNF639敲低后，Snail1、波形蛋白和C-C趋化因子配体20（CCL20）的表达上调，随后CCL20敲低逆转了ZNF639介导的细胞表型变化。
低ZNF639表达是乳腺癌患者无复发生存的一个新的预后因素。
