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Apoptosis. 2017 Mar;22(3):357-368. doi: 10.1007/s10495-016-1323-5.

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

Author information

1
Division of Cancer and Stem Cells, Department of Clinical Oncology, School of Medicine, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
2
Department of Breast and Thyroid Surgery, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
3
Division of Cancer and Stem Cells, Department of Histopathology, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
4
Division of Cancer and Stem Cells, Department of Clinical Oncology, School of Medicine, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK. stewart.martin@nottingham.ac.uk.

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.

KEYWORDS:

Biomarker; Breast cancer; Breast cancer-specific survival; Calpain; Caspase

PMID:
27798717
PMCID:
PMC5306438
DOI:
10.1007/s10495-016-1323-5
[Indexed for MEDLINE]
Free PMC Article

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