Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

Purpose: To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. Methods: Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients elig...

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Autores principales:	Max A.A. Ragusi, Tycho Bismeijer, Bas H.M. van der Velden, Claudette E. Loo, Sander Canisius, Jelle Wesseling, Lodewyk F.A. Wessels, Sjoerd G. Elias, Kenneth G.A. Gilhuijs
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Breast neoplasm Magnetic resonance imaging Gene expression Proteasome endopeptidase complex Parenchymal tissue Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a7a1e711194c46f9bfc41983bd3be40b
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spelling	oai:doaj.org-article:a7a1e711194c46f9bfc41983bd3be40b2021-11-10T04:18:02ZContralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients1532-308010.1016/j.breast.2021.11.002https://doaj.org/article/a7a1e711194c46f9bfc41983bd3be40b2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S096097762100984Xhttps://doaj.org/toc/1532-3080Purpose: To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. Methods: Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355). Results: CPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS. Conclusion: CPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.Max A.A. RagusiTycho BismeijerBas H.M. van der VeldenClaudette E. LooSander CanisiusJelle WesselingLodewyk F.A. WesselsSjoerd G. EliasKenneth G.A. GilhuijsElsevierarticleBreast neoplasmMagnetic resonance imagingGene expressionProteasome endopeptidase complexParenchymal tissueNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast, Vol 60, Iss , Pp 230-237 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Breast neoplasm Magnetic resonance imaging Gene expression Proteasome endopeptidase complex Parenchymal tissue Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Breast neoplasm Magnetic resonance imaging Gene expression Proteasome endopeptidase complex Parenchymal tissue Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Max A.A. Ragusi Tycho Bismeijer Bas H.M. van der Velden Claudette E. Loo Sander Canisius Jelle Wesseling Lodewyk F.A. Wessels Sjoerd G. Elias Kenneth G.A. Gilhuijs Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients
description	Purpose: To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. Methods: Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355). Results: CPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS. Conclusion: CPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.
format	article
author	Max A.A. Ragusi Tycho Bismeijer Bas H.M. van der Velden Claudette E. Loo Sander Canisius Jelle Wesseling Lodewyk F.A. Wessels Sjoerd G. Elias Kenneth G.A. Gilhuijs
author_facet	Max A.A. Ragusi Tycho Bismeijer Bas H.M. van der Velden Claudette E. Loo Sander Canisius Jelle Wesseling Lodewyk F.A. Wessels Sjoerd G. Elias Kenneth G.A. Gilhuijs
author_sort	Max A.A. Ragusi
title	Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients
title_short	Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients
title_full	Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients
title_fullStr	Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients
title_full_unstemmed	Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients
title_sort	contralateral parenchymal enhancement on mri is associated with tumor proteasome pathway gene expression and overall survival of early er+/her2-breast cancer patients
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a7a1e711194c46f9bfc41983bd3be40b
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Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

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