Cell division cycle 25C (CDC25C) expression confers poor prognosis in invasive breast cancer

Ojiegbe, S. and Joseph, C. and Provenzano, E. and Caldas, C. and Nolan, C. and Green, A.R. and Rakha, E. and Ellis, I.O. and Mukherjee, A. (2017) Cell division cycle 25C (CDC25C) expression confers poor prognosis in invasive breast cancer. In: Belfast Pathology 2017: 10th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 20-23 June 2017, Belfast, United Kingdom.

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Background: CDC25C, belonging to the Cdc25 phosphatase family, plays a major role in cell cycle control, impacting on DNA repair and apoptosis. It has been shown that poor prognosis/copy number high Luminal A breast cancers (BCs) are enriched for the Aurora kinase pathway including CDC25C leading to CDK1 activation (Ciriello et al, Breast Cancer Research Treatment, 2013:409). This study examined the associations of CDC25C with clinicopathological and molecular features in BCs including the low grade ER positive cohort.

Methodology: CDC25C mRNA expression was studied in the METABRIC BC cohort (n=1980) and externally validated using online expression datasets [bc-GenExMiner v4.0]. CDC25C protein expression level was assessed immunohistochemically on a large annotated series of BC (n= 1330) and correlations made with clinicopathological parameters and patient outcome.

Results: High CDC25C expression was significantly associated with poor prognostic factors including high grade, large tumour size, medullary like tumours, poorer NPI, ER-/PR- Her2+ status (p<0.001) and was differentially expressed in poor prognosis integrative clusters 5 and 10 (p<0.001). Cytoplasmic CDC25C (c-CDC25C) protein showed positive association with non-NST and non-medullary tumour subtypes while nuclear CDC25C (n-CDC25C) negatively associated with tumour stage (p<0.05). There was no association with ER, PR status, NPI and lymph nodes. However, high c-CDC25C resulted in poor survival at 20 years in the Grade 1 ER+ cohort (p=0.007), while high n-CDC25C showed better long term survival (p<0.001). Pooled CDC25C expression data in the external validation cohort showed an association with poor outcome (p<0.0001, HR = 1.45, 95 % CI 1.28—1.64).

Conclusion: CDC25C appears to be associated with poor prognosis in BC including the Grade 1 ER+ cohort, indicating the importance of further functional analyses.

Item Type: Conference or Workshop Item (Paper)
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Depositing User: Mukherjee, Abhik
Date Deposited: 07 Jul 2017 09:37
Last Modified: 12 Oct 2017 23:50
URI: https://eprints.nottingham.ac.uk/id/eprint/43999

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