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Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364763 | PMC |
| http://dx.doi.org/10.1007/s11596-025-00081-9 | DOI Listing |
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