Insights into the prognostic significance of cell division cycle 25A (CDC25A) in breast cancer

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BACKGROUND: Cell division cycle 25A (CDC25A) is a key regulator of cell cycle progression, DNA replication and apoptosis in cancer cells. This study employed multiple well-characterised breast cancer cohorts to evaluate the prognostic significance of CDC25A and to characterise the molecular association linked to its expression in early-stage breast cancer. METHODS: CDC25A transcriptomic expression was systematically assessed for statistical associations with key genes and pathways implicated in cell cycle regulation, DNA damage repair, cyclin-dependent signalling, tumour microenvironment and epithelial-mesenchymal transition. Its prognostic relevance was further evaluated through survival analyses. These investigations were conducted across the Molecular Taxonomy of Breast Cancer International Consortium (n=1980), the Cancer Genome Atlas (n=854) and Kaplan-Meier Plotter (n=4929) breast cancer cohorts. Subsequently, this study explored the associations between CDC25A protein expression and established clinicopathological parameters, molecular characteristics and patient outcomes using immunohistochemistry in a large, well-characterised Nottingham breast cancer cohort (n=1045). RESULTS: High CDC25A expression was associated with altered expression of key breast cancer-related genes involved in cell cycle control, DNA damage repair, cyclin-dependent signalling, matrix remodelling and epithelial-mesenchymal transition-related biology. Elevated CDC25A expression at both transcriptomic and proteomic levels was significantly associated with aggressive clinicopathological features, including higher tumour grade, larger tumour size, hormone receptor negativity and lymphovascular invasion. High CDC25A protein expression independently predicted poorer survival outcomes (p=0.027; HR 1.28, 95% CI 1.18 to 1.98). CONCLUSION: CDC25A is an independent prognostic biomarker of clinical outcome in breast cancer. Further functional studies are warranted to validate CDC25A as a potential prognostic and therapeutic biomarker in breast cancer.

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