QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation

Triple-negative breast cancer (TNBC) can be further classified into androgen receptor (AR)-positive TNBC and AR-negative TNBC or quadruple-negative breast cancer (QNBC). Here, we investigated genomic instability in 53 clinical cases by array-CGH and miRNA expression profiling. Immunohistochemical an...

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Autores principales:	Shristi Bhattarai, Bruna M. Sugita, Stefanne M. Bortoletto, Aline S. Fonseca, Luciane R. Cavalli, Ritu Aneja
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	triple-negative breast cancer quadruple-negative breast cancer AR loss genomic instability copy number array-CGH Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f71df66240004edba2369d048b0f563a
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spelling	oai:doaj.org-article:f71df66240004edba2369d048b0f563a2021-11-11T17:01:21ZQNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation10.3390/ijms2221115481422-00671661-6596https://doaj.org/article/f71df66240004edba2369d048b0f563a2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11548https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Triple-negative breast cancer (TNBC) can be further classified into androgen receptor (AR)-positive TNBC and AR-negative TNBC or quadruple-negative breast cancer (QNBC). Here, we investigated genomic instability in 53 clinical cases by array-CGH and miRNA expression profiling. Immunohistochemical analysis revealed that 64% of TNBC samples lacked AR expression. This group of tumors exhibited a higher level of copy number alterations (CNAs) and a higher frequency of cases affected by CNAs than TNBCs. CNAs in genes of the chromosome instability 25 (CIN25) and centrosome amplification (CA) signatures were more frequent in the QNBCs and were similar between the groups, respectively. However, expression levels of CIN25 and CA20 genes were higher in QNBCs. miRNA profiling revealed 184 differentially expressed miRNAs between the groups. Fifteen of these miRNAs were mapped at cytobands with CNAs, of which eight (miR-1204, miR-1265, miR-1267, miR-23c, miR-548ai, miR-567, miR-613, and miR-943), and presented concordance of expression and copy number levels. Pathway enrichment analysis of these miRNAs/mRNAs pairings showed association with genomic instability, cell cycle, and DNA damage response. Furthermore, the combined expression of these eight miRNAs robustly discriminated TNBCs from QNBCs (AUC = 0.946). Altogether, our results suggest a significant loss of AR in TNBC and a profound impact in genomic instability characterized by CNAs and deregulation of miRNA expression.Shristi BhattaraiBruna M. SugitaStefanne M. BortolettoAline S. FonsecaLuciane R. CavalliRitu AnejaMDPI AGarticletriple-negative breast cancerquadruple-negative breast cancerAR lossgenomic instabilitycopy numberarray-CGHBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11548, p 11548 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	triple-negative breast cancer quadruple-negative breast cancer AR loss genomic instability copy number array-CGH Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	triple-negative breast cancer quadruple-negative breast cancer AR loss genomic instability copy number array-CGH Biology (General) QH301-705.5 Chemistry QD1-999 Shristi Bhattarai Bruna M. Sugita Stefanne M. Bortoletto Aline S. Fonseca Luciane R. Cavalli Ritu Aneja QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation
description	Triple-negative breast cancer (TNBC) can be further classified into androgen receptor (AR)-positive TNBC and AR-negative TNBC or quadruple-negative breast cancer (QNBC). Here, we investigated genomic instability in 53 clinical cases by array-CGH and miRNA expression profiling. Immunohistochemical analysis revealed that 64% of TNBC samples lacked AR expression. This group of tumors exhibited a higher level of copy number alterations (CNAs) and a higher frequency of cases affected by CNAs than TNBCs. CNAs in genes of the chromosome instability 25 (CIN25) and centrosome amplification (CA) signatures were more frequent in the QNBCs and were similar between the groups, respectively. However, expression levels of CIN25 and CA20 genes were higher in QNBCs. miRNA profiling revealed 184 differentially expressed miRNAs between the groups. Fifteen of these miRNAs were mapped at cytobands with CNAs, of which eight (miR-1204, miR-1265, miR-1267, miR-23c, miR-548ai, miR-567, miR-613, and miR-943), and presented concordance of expression and copy number levels. Pathway enrichment analysis of these miRNAs/mRNAs pairings showed association with genomic instability, cell cycle, and DNA damage response. Furthermore, the combined expression of these eight miRNAs robustly discriminated TNBCs from QNBCs (AUC = 0.946). Altogether, our results suggest a significant loss of AR in TNBC and a profound impact in genomic instability characterized by CNAs and deregulation of miRNA expression.
format	article
author	Shristi Bhattarai Bruna M. Sugita Stefanne M. Bortoletto Aline S. Fonseca Luciane R. Cavalli Ritu Aneja
author_facet	Shristi Bhattarai Bruna M. Sugita Stefanne M. Bortoletto Aline S. Fonseca Luciane R. Cavalli Ritu Aneja
author_sort	Shristi Bhattarai
title	QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation
title_short	QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation
title_full	QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation
title_fullStr	QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation
title_full_unstemmed	QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation
title_sort	qnbc is associated with high genomic instability characterized by copy number alterations and mirna deregulation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f71df66240004edba2369d048b0f563a
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QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation

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