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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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11548 |
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| 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 |
| collection | DOAJ |
| 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. |
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| language | English |
| last_indexed | 2024-03-10T06:02:14Z |
| publishDate | 2021-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f71df66240004edba2369d048b0f563a2023-11-22T20:54:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211154810.3390/ijms222111548QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA DeregulationShristi Bhattarai0Bruna M. Sugita1Stefanne M. Bortoletto2Aline S. Fonseca3Luciane R. Cavalli4Ritu Aneja5Department of Biology, Georgia State University, Atlanta, GA 30303, USAResearch Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba 80250-060, BrazilResearch Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba 80250-060, BrazilResearch Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba 80250-060, BrazilResearch Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba 80250-060, BrazilDepartment of Biology, Georgia State University, Atlanta, GA 30303, USATriple-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.https://www.mdpi.com/1422-0067/22/21/11548triple-negative breast cancerquadruple-negative breast cancerAR lossgenomic instabilitycopy numberarray-CGH |
| spellingShingle | 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 International Journal of Molecular Sciences triple-negative breast cancer quadruple-negative breast cancer AR loss genomic instability copy number array-CGH |
| title | 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_short | 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 |
| topic | triple-negative breast cancer quadruple-negative breast cancer AR loss genomic instability copy number array-CGH |
| url | https://www.mdpi.com/1422-0067/22/21/11548 |
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