乳腺癌患者ZWINT表达与临床病理特征及预后的关系

IF 2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Medical Science Pub Date : 2025-07-01 DOI:10.1007/s11596-025-00081-9

Bei Liu, Qin Wang, Xiao-Hong Min, Han-Han Liu, Huan Wu, Hui Xu, Jun-Bo Hu, Yong-Qing Tong, Zi-Ming Huang

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引用次数: 0

摘要

目的：ZW10相互作用着丝粒蛋白（ZWINT）已被证实在肿瘤的生长、侵袭和迁移中起关键作用。然而，ZWINT的表达水平是否与乳腺癌患者的临床病理特征和预后有显著相关性尚不清楚。本研究通过整合分子分型和生存分析，系统探讨ZWINT在乳腺癌中表达的临床意义。方法：采用多组学分析的综合生物信息学方法，系统地表征了ZWINT在不同乳腺癌亚型中的空间表达模式，并评估了其预后意义。该方法包括Breast Cancer Gene-Expression Miner v5.1 (bc-GenExMiner v5.1), TNMplot, muttarget， PrognoScan数据库和database for Annotation， Visualization, and Integrated Discovery （DAVID）。结果：我们的分析显示，在不同的乳腺癌临床病理亚型中，ZWINT mRNA和蛋白的表达一致上调。ZWINT过表达与cadherin 1 （CDH1）和肿瘤蛋白p53 （TP53）的截断突变显著共存，提示在肿瘤进展途径中存在潜在的功能串扰。ZWINT过表达与不良临床结果相关，显示死亡风险增加48%（总生存期：HR 1.48, 95% CI 1.23-1.79），复发概率增加66%（无复发生存期：1.66,95% CI 1.50-1.84），转移风险增加63%（无远处转移生存期：HR 1.63, 95% CI 1.39-1.90）。结合TNM分期和分子亚型的多因素Cox回归证实了ZWINT是独立的预后决定因素(P结论：ZWINT可能与TP53/CDH1一起作为乳腺癌预后的潜在生物标志物和可能的治疗靶点。

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Association of ZWINT Expression with Clinicopathologic Characteristics and Prognosis in Breast Cancer Patients.

Objective: ZW10 interacting kinetochore protein (ZWINT) has been demonstrated to play a pivotal role in the growth, invasion, and migration of cancers. Nevertheless, whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive. This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.

Methods: We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis. The approach included the Breast Cancer Gene-Expression Miner v5.1 (bc-GenExMiner v5.1), TNMplot, MuTarget, PrognoScan database, and Database for Annotation, Visualization, and Integrated Discovery (DAVID).

Results: Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer. ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1 (CDH1) and tumor protein p53 (TP53), suggesting potential functional crosstalk in tumor progression pathways. The overexpression of ZWINT correlated with adverse clinical outcomes, showing 48% increased mortality risk (overall survival: HR 1.48, 95% CI 1.23-1.79), 66% higher recurrence probability (relapse-free survival: 1.66, 95% CI 1.50-1.84), and 63% elevated metastasis risk (distant metastasis-free survival: HR 1.63, 95% CI 1.39-1.90). Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant (P < 0.001, Harrell's C-index = 0.7827), which was validated through bootstrap resampling (1000 iterations).

Conclusion: ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.

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来源期刊

Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.70

自引率

0.00%

发文量

126

期刊介绍： Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.