SARAH STORR sarah.storr@nottingham.ac.uk
Assistant Professor
The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy
Storr, Sarah J.; Zhang, Siwei; Perren, Tim; Lansdown, Mark; Fatayer, Hiba; Sharma, Nisha; Gahlaut, Renu; Shaaban, Abeer; Martin, Stewart G.
Authors
Siwei Zhang
Tim Perren
Mark Lansdown
Hiba Fatayer
Nisha Sharma
Renu Gahlaut
Abeer Shaaban
Stewart G. Martin
Abstract
The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.
The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.
Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total patient cohort; however, in patients with non-inflammatory breast cancer, high calpastatin expression was significantly associated with adverse breast cancer-specific survival (P=0.035), as was low calpain-2 expression (P=0.031). Low calpastatin expression was significantly associated with adverse breast cancer-specific survival of the inflammatory breast cancer patients (P=0.020), as was low calpain-1 expression (P=0.003).
In conclusion, high calpain-2 and low calpastatin expression is associated with improved breast cancer-specific survival in non-inflammatory large but operable primary breast cancer treated with neoadjuvant chemotherapy. In inflammatory cases, high calpain-1 and high calpastatin expression is associated with improved breast cancer-specific survival. Determining the expression of these proteins may be of clinical relevance. Further validation, in multi-centre cohorts of breast cancer patients treated with neoadjuvant chemotherapy, is warranted.
Citation
Storr, S. J., Zhang, S., Perren, T., Lansdown, M., Fatayer, H., Sharma, N., …Martin, S. G. (2016). The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy. Oncotarget, 7(30), 47927-47937. https://doi.org/10.18632/oncotarget.10066
Journal Article Type | Article |
---|---|
Acceptance Date | May 29, 2016 |
Online Publication Date | Jun 15, 2016 |
Publication Date | Jun 15, 2016 |
Deposit Date | Jun 7, 2016 |
Publicly Available Date | Aug 15, 2018 |
Journal | Oncotarget |
Electronic ISSN | 1949-2553 |
Publisher | Impact Journals |
Peer Reviewed | Peer Reviewed |
Volume | 7 |
Issue | 30 |
Pages | 47927-47937 |
DOI | https://doi.org/10.18632/oncotarget.10066 |
Keywords | Calpain; Calpastatin; Breast cancer; Neoadjuvant chemotherapy; Survival |
Public URL | https://nottingham-repository.worktribe.com/output/795086 |
Publisher URL | http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=10066&author-preview=7rm |
Contract Date | Jun 7, 2016 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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