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

IF 2.4 4区医学 Q3 ONCOLOGY Journal of Breast Cancer Pub Date : 2025-04-01 Epub Date: 2025-03-09 DOI:10.4048/jbc.2024.0224

Fang Lee, Shih-Ping Cheng, Ming-Jen Chen, Wen-Chien Huang, Yi-Min Liu, Shao-Chiang Chang, Yuan-Ching Chang

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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.

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锌指蛋白639的表达是乳腺癌预后的一个新的决定因素。

目的：锌指蛋白639 （ZNF639）常存在于PIK3CA重叠扩增子中，既往研究提示其参与食管癌和口腔鳞状细胞癌的发病机制。然而，其在乳腺癌中的表达和意义尚不明确。方法：采用组织芯片技术对ZNF639进行免疫组化分析。通过转染小干扰RNA，对敲低ZNF639的乳腺肿瘤细胞进行集落形成、Transwell细胞迁移和体内转移等功能研究。结果：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的表达与良好的生存结果相关，包括无复发生存(风险比，0.35；95%可信区间[CI]， 0.14-0.89)和总生存率(风险比，0.41；95% ci, 0.16-1.05)。ZNF639敲除增加NOD/SCID小鼠的克隆原性、细胞运动性和肺转移。在敲低ZNF639后，Snail1、vimentin和C-C趋化因子配体20 （CCL20）的表达上调，并通过随后敲低CCL20逆转ZNF639介导的细胞表型变化。结论：低表达的ZNF639是乳腺癌患者无复发生存的一个新的预后因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Breast Cancer 医学-肿瘤学

CiteScore

3.80

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal of Breast Cancer (abbreviated as ''J Breast Cancer'') is the official journal of the Korean Breast Cancer Society, which is issued quarterly in the last day of March, June, September, and December each year since 1998. All the contents of the Journal is available online at the official journal website (http://ejbc.kr) under open access policy. The journal aims to provide a forum for the academic communication between medical doctors, basic science researchers, and health care professionals to be interested in breast cancer. To get this aim, we publish original investigations, review articles, brief communications including case reports, editorial opinions on the topics of importance to breast cancer, and welcome new research findings and epidemiological studies, especially when they contain a regional data to grab the international reader''s interest. Although the journal is mainly dealing with the issues of breast cancer, rare cases among benign breast diseases or evidence-based scientifically written articles providing useful information for clinical practice can be published as well.