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A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease

Storr, Sarah J.; Hoskin, Victoria; Aiyappa‐Maudsley, Radhika; Ghaffari, Abdi; Varma, Sonal; Green, Andrew; Rakha, Emad; Ellis, Ian O.; Greer, Peter A.; Martin, Stewart G.

A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease Thumbnail


Authors

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

Victoria Hoskin

Radhika Aiyappa‐Maudsley

Abdi Ghaffari

Sonal Varma

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology

Peter A. Greer

STEWART MARTIN STEWART.MARTIN@NOTTINGHAM.AC.UK
Professor of Cancer and Radiation Biology



Abstract

Introduction: The cytoskeletal protein ezrin is upregulated in many cancer types and is strongly associated with poor patient outcome. While the clinical and prognostic value of ezrin has been previously evaluated in breast cancer, most studies to date have been conducted in smaller cohorts (less than 500 cases) or have focused on specific disease characteristics. The current study is the largest of its kind to evaluate ezrin both at the protein and mRNA levels in early-stage breast cancer patients using the Nottingham (n=1094) and METABRIC (n=1980) cohorts, respectively. Results: High expression of ezrin was significantly associated with larger tumour size (p=0.027), higher tumour grade (p < 0.001), worse Nottingham Prognostic Index prognostic group (p=0.011) and HER2-positive status (p=0.001). High ezrin expression was significantly associated with adverse survival of breast cancer patients (p < 0.001) and remained associated with survival in multivariate Cox-regression analysis (p=0.018, hazard ratio (HR)=1.343, 95% confidence interval (CI)=1.051–1.716) when potentially confounding factors were included. High ezrin expression was significantly associated with adverse survival of patients whose tumours were categorised as receptor (oestrogen receptor (ER), progesterone receptor (PgR) or HER2) positive (p < 0.001) in comparison to those categorised as triple-negative breast cancer (p=0.889). High expression of ezrin mRNA (VIL2) in the METABRIC cohort was also significantly associated with adverse survival of breast cancer patients (p < 0.001). Conclusion: Retrospective analyses show that ezrin is an independent prognostic marker, with higher expression associated with shortened survival in receptor-positive (ER, PgR or HER2) patients. Ezrin expression is associated with more aggressive disease and may have clinical utility as a biomarker of patient prognosis in early-stage breast cancer.

Citation

Storr, S. J., Hoskin, V., Aiyappa‐Maudsley, R., Ghaffari, A., Varma, S., Green, A., …Martin, S. G. (2023). A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease. Cancer Medicine, 12(9), 10908-10916. https://doi.org/10.1002/cam4.5802

Journal Article Type Article
Acceptance Date Feb 27, 2023
Online Publication Date Mar 20, 2023
Publication Date 2023-05
Deposit Date May 16, 2023
Publicly Available Date Mar 29, 2024
Journal Cancer Medicine
Electronic ISSN 2045-7634
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 12
Issue 9
Pages 10908-10916
DOI https://doi.org/10.1002/cam4.5802
Keywords Breast cancer, EZR, ezrin, VIL2
Public URL https://nottingham-repository.worktribe.com/output/18804840
Publisher URL https://onlinelibrary.wiley.com/doi/10.1002/cam4.5802
Additional Information This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

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