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

Xuan, Pu; Storr, Sarah J.; Zhang, Yimin; Rakha, Emad; Green, Andrew R.; Ellis, Ian O.; Martin, Stewart G.


Pu Xuan

Sarah J. Storr

Yimin Zhang

Professor of Breast Cancer Pathology

Andrew R. Green

Ian O. Ellis

Stewart G. Martin


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.


Xuan, P., Storr, S. J., Zhang, Y., Rakha, E., Green, A. R., Ellis, I. O., & Martin, S. G. (in press). Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival. Apoptosis,

Journal Article Type Article
Acceptance Date Oct 25, 2016
Online Publication Date Oct 31, 2016
Deposit Date Jan 12, 2017
Publicly Available Date Jan 12, 2017
Journal Apoptosis
Print ISSN 1360-8185
Electronic ISSN 1573-675X
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Keywords Breast cancer, Caspase, Calpain, Breast cancer-specific survival, Biomarker
Public URL
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art%3A10.1007%2Fs10495-016-1323-5.pdf (1.6 Mb)

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