Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival
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 caspas...
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| Format: | Article |
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Springer Verlag
2016
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| Online Access: | https://eprints.nottingham.ac.uk/39796/ |
| _version_ | 1848795915536564224 |
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| author | Xuan, Pu Storr, Sarah J. Zhang, Yimin Rakha, Emad Green, Andrew R. Ellis, Ian O. Martin, Stewart G. |
| author_facet | Xuan, Pu Storr, Sarah J. Zhang, Yimin Rakha, Emad Green, Andrew R. Ellis, Ian O. Martin, Stewart G. |
| author_sort | Xuan, Pu |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:39:40Z |
| format | Article |
| id | nottingham-39796 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:39:40Z |
| publishDate | 2016 |
| publisher | Springer Verlag |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-397962020-05-04T18:14:53Z https://eprints.nottingham.ac.uk/39796/ 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. 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. Springer Verlag 2016-10-31 Article PeerReviewed Xuan, Pu, Storr, Sarah J., Zhang, Yimin, Rakha, Emad, Green, Andrew R., 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 Breast cancer Caspase Calpain Breast cancer-specific survival Biomarker http://link.springer.com/article/10.1007%2Fs10495-016-1323-5 doi:10.1007/s10495-016-1323-5 doi:10.1007/s10495-016-1323-5 |
| spellingShingle | Breast cancer Caspase Calpain Breast cancer-specific survival Biomarker Xuan, Pu Storr, Sarah J. Zhang, Yimin Rakha, Emad Green, Andrew R. Ellis, Ian O. Martin, Stewart G. Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival |
| title | Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival |
| title_full | Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival |
| title_fullStr | Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival |
| title_full_unstemmed | Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival |
| title_short | Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival |
| title_sort | caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival |
| topic | Breast cancer Caspase Calpain Breast cancer-specific survival Biomarker |
| url | https://eprints.nottingham.ac.uk/39796/ https://eprints.nottingham.ac.uk/39796/ https://eprints.nottingham.ac.uk/39796/ |