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.

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.

Citation

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, https://doi.org/10.1007/s10495-016-1323-5

• 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
• DOI: https://doi.org/10.1007/s10495-016-1323-5
• Keywords: Breast cancer, Caspase, Calpain, Breast cancer-specific survival, Biomarker
• Public URL: https://nottingham-repository.worktribe.com/output/820939
• Publisher URL: http://link.springer.com/article/10.1007%2Fs10495-016-1323-5
• Contract Date: Jan 12, 2017