Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival

Xuan, Pu and Storr, Sarah J. and Zhang, Yimin and Rakha, Emad and Green, Andrew R. and Ellis, Ian O. and Martin, Stewart G. (2016) Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival. Apoptosis . pp. 1-12. ISSN 1573-675X

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Abstract

Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry on tissue microarrays. High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively). Multivariate analysis showed that caspase-3 remained an independent factor when confounding factors were included (hazard ratio (HR) 1.347, 95% confidence interval (CI) 1.086–1.670; P = 0.007). The analyses in individual subgroups demonstrated the significance of caspase-3 expression in clinical outcomes in receptor positive (ER, PR or HER2) subgroups (P = 0.001) and in non-basal like subgroup (P = 0.029). Calpain expression had been previously assessed. Significant association was also found between high caspase-3/high calpain-1 and breast cancer-specific survival in the total patient cohort (P = 0.005) and basal-like subgroup (P = 0.034), as indicated by Kaplan–Meier analysis. Caspase-3 expression is associated with adverse breast cancer-specific survival in breast cancer patients, and provides additional prognostic values in distinct phenotypes. Combinatorial caspase and calpain expression can predict worse prognosis, especially in basal-like phenotypes. The findings warrant further validation studies in independent multi-centre patient cohorts.

Item Type: Article
Keywords: Breast cancer, Caspase, Calpain, Breast cancer-specific survival, Biomarker
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: 10.1007/s10495-016-1323-5
Depositing User: Eprints, Support
Date Deposited: 12 Jan 2017 11:38
Last Modified: 14 Oct 2017 11:20
URI: http://eprints.nottingham.ac.uk/id/eprint/39796

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