1. Low cleaved caspase-7 levels indicate unfavourable outcome across all breast cancers
- Author
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Damir Varešlija, Brona M. Murphy, Andreas U. Lindner, Alexa Resler, Arnold D.K. Hill, Federico Lucantoni, Leonie S. Young, William M. Gallagher, and Jochen H. M. Prehn
- Subjects
0301 basic medicine ,Oncology ,Programmed cell death ,medicine.medical_specialty ,Breast Neoplasms ,Caspase 7 ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,hemic and lymphatic diseases ,Internal medicine ,Drug Discovery ,Caspase activation ,Biomarkers, Tumor ,medicine ,Humans ,Genetics (clinical) ,Triple-negative breast cancer ,Caspase ,biology ,business.industry ,Prognosis ,medicine.disease ,Molecular medicine ,3. Good health ,030104 developmental biology ,Proto-Oncogene Proteins c-bcl-2 ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Female ,business - Abstract
Elevated levels of the anti-apoptotic BCL2 protein associate with favourable outcome in breast cancer. We investigated whether executioner caspase activation downstream of mitochondrial apoptosis was associated with, or independent, of BCL2's prognostic signature in breast cancer. Levels of pro- and anti-apoptotic BCL2 family proteins were quantified in triple negative breast cancer (TNBC) samples and utilised to calculate BCL2 profiles of 845 breast cancer patients. Biomarkers including single apoptosis proteins and network-enriched apoptosis system signatures were evaluated using uni- and multi-variate Cox-models. In both TNBC and non-TNBC breast cancer, the anti-apoptotic BCL2 protein was particularly abundant when compared to other solid tumours. High BCL2 protein levels were prognostic of favourable outcome across all breast cancers (HR 0.4, 95% CI 0.2-0.6, Wald p 0.0001). Although BCL2 and cleaved caspase-7 levels were negatively correlated, levels of cleaved caspase-7 were also associated with favourable outcome (HR 0.4, 95% CI 0.3-0.7, Wald p = 0.001). A combination of low BCL2 and low cleaved caspase-7 protein levels was highly prognostic of unfavourable outcome across all breast cancers (HR 11.29, 95% CI 2.20-58.23, Wald p = 0.01). A combination of BCL2 and cleaved caspase-7 levels is a promising prognostic biomarker in breast cancer patients.BCL2 levels are elevated in breast cancer where they are marker of good prognosis. BCL2 and active caspase levels correlate negatively; yet, active caspases indicate good outcome. Low BCL2 and low caspase-7 are highly prognostic of unfavourable outcome across all breast cancers. BCL2 levels indicate molecular subtype and tumour proliferation status in breast cancer.
- Published
- 2018
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