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

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...

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Main Authors: Sarah J. Storr, Victoria Hoskin, Radhika Aiyappa‐Maudsley, Abdi Ghaffari, Sonal Varma, Andrew Green, Emad Rakha, Ian O. Ellis, Peter A. Greer, Stewart G. Martin
Format: Article
Language:English
Published: Wiley 2023-05-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.5802
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author Sarah J. Storr
Victoria Hoskin
Radhika Aiyappa‐Maudsley
Abdi Ghaffari
Sonal Varma
Andrew Green
Emad Rakha
Ian O. Ellis
Peter A. Greer
Stewart G. Martin
author_facet Sarah J. Storr
Victoria Hoskin
Radhika Aiyappa‐Maudsley
Abdi Ghaffari
Sonal Varma
Andrew Green
Emad Rakha
Ian O. Ellis
Peter A. Greer
Stewart G. Martin
author_sort Sarah J. Storr
collection DOAJ
description 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.
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spelling doaj.art-c970806911ed436fa210b513806aa37c2023-05-28T20:33:59ZengWileyCancer Medicine2045-76342023-05-01129109081091610.1002/cam4.5802A 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 diseaseSarah J. Storr0Victoria Hoskin1Radhika Aiyappa‐Maudsley2Abdi Ghaffari3Sonal Varma4Andrew Green5Emad Rakha6Ian O. Ellis7Peter A. Greer8Stewart G. Martin9Nottingham Breast Cancer Research Centre, Biodiscovery Institute University of Nottingham, School of Medicine Nottingham UKDivision of Cancer Biology and Genetics, Queen's Cancer Research Institute Queen's University Kingston Ontario CanadaNottingham Breast Cancer Research Centre, Biodiscovery Institute University of Nottingham, School of Medicine Nottingham UKDivision of Cancer Biology and Genetics, Queen's Cancer Research Institute Queen's University Kingston Ontario CanadaDepartment of Pathology and Molecular Medicine Queen's University Kingston Ontario CanadaNottingham Breast Cancer Research Centre, Biodiscovery Institute University of Nottingham, School of Medicine Nottingham UKNottingham Breast Cancer Research Centre, Biodiscovery Institute University of Nottingham, School of Medicine Nottingham UKNottingham Breast Cancer Research Centre, Biodiscovery Institute University of Nottingham, School of Medicine Nottingham UKDivision of Cancer Biology and Genetics, Queen's Cancer Research Institute Queen's University Kingston Ontario CanadaNottingham Breast Cancer Research Centre, Biodiscovery Institute University of Nottingham, School of Medicine Nottingham UKAbstract 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.https://doi.org/10.1002/cam4.5802breast cancerEZRezrinVIL2
spellingShingle Sarah J. Storr
Victoria Hoskin
Radhika Aiyappa‐Maudsley
Abdi Ghaffari
Sonal Varma
Andrew Green
Emad Rakha
Ian O. Ellis
Peter A. Greer
Stewart G. Martin
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
breast cancer
EZR
ezrin
VIL2
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic breast cancer
EZR
ezrin
VIL2
url https://doi.org/10.1002/cam4.5802
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