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Apoptosis

, Volume 22, Issue 3, pp 357–368

First Online: 31 October 2016DOI: 10.1007-s10495-016-1323-5

Cite this article as: Pu, X., Storr, S.J., Zhang, Y. et al. Apoptosis 2017 22: 357. doi:10.1007-s10495-016-1323-5

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.

KeywordsBreast cancer Caspase Calpain Breast cancer-specific survival Biomarker  Download fulltext PDF



Author: Xuan Pu - Sarah J. Storr - Yimin Zhang - Emad A. Rakha - Andrew R. Green - Ian O. Ellis - Stewart G. Martin

Source: https://link.springer.com/



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