Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes

Abstract Background Cold-inducible RNA-binding protein (CIRBP) is a stress-induced mRNA-binding protein associated with clinical outcomes in a variety of human disease states. The role of CIRBP as a role as a prognostic biomarker in breast cancer (BC) has yet to be established. Findings We describe...

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Main Authors: Matthew Dankner, Veronique Ouellet, Jakob Lafon, Rima Ezzeddine, Matthew G. Annis, Afnan Abu-Thuraia, Quebec Breast Cancer Foundation Tissue Microarray Consortium, Peter M. Siegel
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Breast Cancer Research
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Online Access:https://doi.org/10.1186/s13058-025-02098-3
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author Matthew Dankner
Veronique Ouellet
Jakob Lafon
Rima Ezzeddine
Matthew G. Annis
Afnan Abu-Thuraia
Quebec Breast Cancer Foundation Tissue Microarray Consortium
Peter M. Siegel
author_facet Matthew Dankner
Veronique Ouellet
Jakob Lafon
Rima Ezzeddine
Matthew G. Annis
Afnan Abu-Thuraia
Quebec Breast Cancer Foundation Tissue Microarray Consortium
Peter M. Siegel
author_sort Matthew Dankner
collection DOAJ
description Abstract Background Cold-inducible RNA-binding protein (CIRBP) is a stress-induced mRNA-binding protein associated with clinical outcomes in a variety of human disease states. The role of CIRBP as a role as a prognostic biomarker in breast cancer (BC) has yet to be established. Findings We describe a clinically annotated tissue micro-array cohort of 1406 hormone receptor positive (HR +) and 281 triple negative primary breast cancers (TNBC) stained by immunohistochemistry (IHC) for CIRBP. Statistical analyses were performed with the Kaplan–Meier estimator, as well as univariate and multivariate Cox proportional-hazards models. Multivariate models incorporated tumor size, lymph node status, grade and CIRBP expression levels. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS). In N = 281 primary TNBCs, high levels of CIRBP expression by IHC was associated with poor prognosis in multivariate analysis (OS: adjusted hazard ratio (aHR) 2.05, 95% confidence interval (CI) 1.24–3.41, P = 0.005. PFS: aHR 2.46, 95% CI 1.33–4.57, P = 0.004). However, in N = 1406 HR + primary BC, CIRBP expression was correlated with favorable prognosis (OS: aHR 0.927, 95% CI 0.88–0.98, P = 0.005. PFS: aHR 0.904, 95% CI 0.85–0.96, P = 0.002). Conclusions CIRBP expression is associated with poor prognosis in TNBC but not HR + BC patients. This finding highlights the prognostic significance of CIRBP in TNBC and suggests differential underlying mRNA targets bound and modulated by CIRBP in TNBC and HR + BC, respectively.
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spelling doaj-art-5cc2e5d2da634ae899511f2ee10640c32025-08-24T11:58:47ZengBMCBreast Cancer Research1465-542X2025-08-0127111710.1186/s13058-025-02098-3Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomesMatthew Dankner0Veronique Ouellet1Jakob Lafon2Rima Ezzeddine3Matthew G. Annis4Afnan Abu-Thuraia5Quebec Breast Cancer Foundation Tissue Microarray Consortium6Peter M. Siegel7Rosalind and Morris Goodman Cancer InstituteCentre de Recherche, Centre Hospitalier de L’Université de MontréalDepartment of Medicine, McGill UniversityRosalind and Morris Goodman Cancer InstituteRosalind and Morris Goodman Cancer InstituteRosalind and Morris Goodman Cancer InstituteQuébec Breast Cancer FoundationRosalind and Morris Goodman Cancer InstituteAbstract Background Cold-inducible RNA-binding protein (CIRBP) is a stress-induced mRNA-binding protein associated with clinical outcomes in a variety of human disease states. The role of CIRBP as a role as a prognostic biomarker in breast cancer (BC) has yet to be established. Findings We describe a clinically annotated tissue micro-array cohort of 1406 hormone receptor positive (HR +) and 281 triple negative primary breast cancers (TNBC) stained by immunohistochemistry (IHC) for CIRBP. Statistical analyses were performed with the Kaplan–Meier estimator, as well as univariate and multivariate Cox proportional-hazards models. Multivariate models incorporated tumor size, lymph node status, grade and CIRBP expression levels. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS). In N = 281 primary TNBCs, high levels of CIRBP expression by IHC was associated with poor prognosis in multivariate analysis (OS: adjusted hazard ratio (aHR) 2.05, 95% confidence interval (CI) 1.24–3.41, P = 0.005. PFS: aHR 2.46, 95% CI 1.33–4.57, P = 0.004). However, in N = 1406 HR + primary BC, CIRBP expression was correlated with favorable prognosis (OS: aHR 0.927, 95% CI 0.88–0.98, P = 0.005. PFS: aHR 0.904, 95% CI 0.85–0.96, P = 0.002). Conclusions CIRBP expression is associated with poor prognosis in TNBC but not HR + BC patients. This finding highlights the prognostic significance of CIRBP in TNBC and suggests differential underlying mRNA targets bound and modulated by CIRBP in TNBC and HR + BC, respectively.https://doi.org/10.1186/s13058-025-02098-3CIRBPBreast cancerTNBCEstrogen receptorBiomarker
spellingShingle Matthew Dankner
Veronique Ouellet
Jakob Lafon
Rima Ezzeddine
Matthew G. Annis
Afnan Abu-Thuraia
Quebec Breast Cancer Foundation Tissue Microarray Consortium
Peter M. Siegel
Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes
Breast Cancer Research
CIRBP
Breast cancer
TNBC
Estrogen receptor
Biomarker
title Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes
title_full Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes
title_fullStr Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes
title_full_unstemmed Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes
title_short Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes
title_sort cold inducible rna binding protein is associated with subtype specific breast cancer patient outcomes
topic CIRBP
Breast cancer
TNBC
Estrogen receptor
Biomarker
url https://doi.org/10.1186/s13058-025-02098-3
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