Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.

Defining the aggressiveness and growth rate of a malignant cell population is a key step in the clinical approach to treating tumor disease. The correct grading of breast cancer (BC) is a fundamental part in determining the appropriate treatment. Biological variables can make it difficult to elucida...

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Autores principales:	Claudia Cava, Gloria Bertoli, Marilena Ripamonti, Giancarlo Mauri, Italo Zoppis, Pasquale Anthony Della Rosa, Maria Carla Gilardi, Isabella Castiglioni
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a0b16599b91c44438d5db03e821434ae
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spelling	oai:doaj.org-article:a0b16599b91c44438d5db03e821434ae2021-11-18T08:18:03ZIntegration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.1932-620310.1371/journal.pone.0097681https://doaj.org/article/a0b16599b91c44438d5db03e821434ae2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24866763/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Defining the aggressiveness and growth rate of a malignant cell population is a key step in the clinical approach to treating tumor disease. The correct grading of breast cancer (BC) is a fundamental part in determining the appropriate treatment. Biological variables can make it difficult to elucidate the mechanisms underlying BC development. To identify potential markers that can be used for BC classification, we analyzed mRNAs expression profiles, gene copy numbers, microRNAs expression and their association with tumor grade in BC microarray-derived datasets. From mRNA expression results, we found that grade 2 BC is most likely a mixture of grade 1 and grade 3 that have been misclassified, being described by the gene signature of either grade 1 or grade 3. We assessed the potential of the new approach of integrating mRNA expression profile, copy number alterations, and microRNA expression levels to select a limited number of genomic BC biomarkers. The combination of mRNA profile analysis and copy number data with microRNA expression levels led to the identification of two gene signatures of 42 and 4 altered genes (FOXM1, KPNA4, H2AFV and DDX19A) respectively, the latter obtained through a meta-analytical procedure. The 42-based gene signature identifies 4 classes of up- or down-regulated microRNAs (17 microRNAs) and of their 17 target mRNA, and the 4-based genes signature identified 4 microRNAs (Hsa-miR-320d, Hsa-miR-139-5p, Hsa-miR-567 and Hsa-let-7c). These results are discussed from a biological point of view with respect to pathological features of BC. Our identified mRNAs and microRNAs were validated as prognostic factors of BC disease progression, and could potentially facilitate the implementation of assays for laboratory validation, due to their reduced number.Claudia CavaGloria BertoliMarilena RipamontiGiancarlo MauriItalo ZoppisPasquale Anthony Della RosaMaria Carla GilardiIsabella CastiglioniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97681 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Cava Gloria Bertoli Marilena Ripamonti Giancarlo Mauri Italo Zoppis Pasquale Anthony Della Rosa Maria Carla Gilardi Isabella Castiglioni Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.
description	Defining the aggressiveness and growth rate of a malignant cell population is a key step in the clinical approach to treating tumor disease. The correct grading of breast cancer (BC) is a fundamental part in determining the appropriate treatment. Biological variables can make it difficult to elucidate the mechanisms underlying BC development. To identify potential markers that can be used for BC classification, we analyzed mRNAs expression profiles, gene copy numbers, microRNAs expression and their association with tumor grade in BC microarray-derived datasets. From mRNA expression results, we found that grade 2 BC is most likely a mixture of grade 1 and grade 3 that have been misclassified, being described by the gene signature of either grade 1 or grade 3. We assessed the potential of the new approach of integrating mRNA expression profile, copy number alterations, and microRNA expression levels to select a limited number of genomic BC biomarkers. The combination of mRNA profile analysis and copy number data with microRNA expression levels led to the identification of two gene signatures of 42 and 4 altered genes (FOXM1, KPNA4, H2AFV and DDX19A) respectively, the latter obtained through a meta-analytical procedure. The 42-based gene signature identifies 4 classes of up- or down-regulated microRNAs (17 microRNAs) and of their 17 target mRNA, and the 4-based genes signature identified 4 microRNAs (Hsa-miR-320d, Hsa-miR-139-5p, Hsa-miR-567 and Hsa-let-7c). These results are discussed from a biological point of view with respect to pathological features of BC. Our identified mRNAs and microRNAs were validated as prognostic factors of BC disease progression, and could potentially facilitate the implementation of assays for laboratory validation, due to their reduced number.
format	article
author	Claudia Cava Gloria Bertoli Marilena Ripamonti Giancarlo Mauri Italo Zoppis Pasquale Anthony Della Rosa Maria Carla Gilardi Isabella Castiglioni
author_facet	Claudia Cava Gloria Bertoli Marilena Ripamonti Giancarlo Mauri Italo Zoppis Pasquale Anthony Della Rosa Maria Carla Gilardi Isabella Castiglioni
author_sort	Claudia Cava
title	Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.
title_short	Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.
title_full	Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.
title_fullStr	Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.
title_full_unstemmed	Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.
title_sort	integration of mrna expression profile, copy number alterations, and microrna expression levels in breast cancer to improve grade definition.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a0b16599b91c44438d5db03e821434ae
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Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.

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