Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer

Davis, Jillian; Martin, Stewart G.; Patel, Poulam M.; Green, Andrew R.; Rakha, Emad A.; Ellis, Ian O.; Storr, Sarah J.

Abstract

Background

The calpains are intracellular cysteine proteases that function in a variety of important cellular functions, including signalling, motility, apoptosis and survival. In breast cancer high calpain-1 and calpain-2 expression has been associated with adverse clinical outcome. Calpain-9 was thought to be exclusively expressed in the digestive tract; however recent studies have shown that this protein is also expressed in breast tissue.

Methods

We investigated the expression of calpain-9 in a large cohort of early stage breast cancer patients (n?=?783) using immunohistochemistry on a tissue microarray. Patients had long-term follow-up information available for analysis.

Results

Low expression of calpain-9 was associated with patients over 40 years of age (P?=?0.025), smaller tumour size (P?=?0.001), lower tumour stage (P?=?0.009), a more favourable Nottingham Prognostic Index value (P?=?0.002) and positive oestrogen receptor status (P?=?0.014). Calpain-9 expression was not associated with survival in the total patient cohort, however low calpain-9 expression was associated with adverse survival in patients who received endocrine therapy (P?=?0.033), which remained significant in multivariate Cox regression analysis accounting for potential confounding factors (hazard ratio (HR)?=?0.56, 95% confidence interval (95% CI)?=?0.36-0.89, P?=?0.013). Low calpain-9 expression was also associated with adverse survival in patients with an intermediate Nottingham Prognostic Index value (P?=?0.009), and remained so in multivariate analysis (HR?=?0.54, 95% CI?=?0.36-0.82, P?=?0.003).

Conclusions

This study suggests that calpain-9 may play a role in breast cancer and that low expression is associated with poorer patient clinical outcome following endocrine therapy. Validation studies are warranted as determining expression of calpain-9 may provide important prognostic information.

• Journal Article Type: Article
• Acceptance Date: Dec 16, 2014
• Publication Date: Dec 23, 2014
• Deposit Date: Aug 14, 2018
• Publicly Available Date: Oct 17, 2018
• Electronic ISSN: 1471-2407
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 1
• Article Number: 995
• DOI: https://doi.org/10.1186/1471-2407-14-995
• Public URL: https://nottingham-repository.worktribe.com/output/1101198
• Publisher URL: https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-14-995
• PMID: 25539577