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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

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SARAH STORR sarah.storr@nottingham.ac.uk
Assistant Professor

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 Mar 28, 2024
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

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