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A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer
BACKGROUND: To investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC). METHODS: Twenty-five samples of AA TNBC patients were pr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317413/ https://www.ncbi.nlm.nih.gov/pubmed/34315420 http://dx.doi.org/10.1186/s12885-021-08573-2 |
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author | Turkistani, Safaa Sugita, Bruna M. Fadda, Paolo Marchi, Rafael Afsari, Ali Naab, Tammey Apprey, Victor Copeland, Robert L. Campbell, Michael C. Cavalli, Luciane R. Kanaan, Yasmine |
author_facet | Turkistani, Safaa Sugita, Bruna M. Fadda, Paolo Marchi, Rafael Afsari, Ali Naab, Tammey Apprey, Victor Copeland, Robert L. Campbell, Michael C. Cavalli, Luciane R. Kanaan, Yasmine |
author_sort | Turkistani, Safaa |
collection | PubMed |
description | BACKGROUND: To investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC). METHODS: Twenty-five samples of AA TNBC patients were profiled for global miRNA expression and stratified considering three clinical-pathological parameters: tumor size, lymph node (LN), and recurrence (REC) status. Differential miRNA expression analysis was performed for each parameter, and their discriminatory power was determined by Receiver Operating Characteristic (ROC) curve analysis. KMplotter was assessed to determine the association of the miRNAs with survival, and functional enrichment analysis to determine the main affected pathways and miRNA/mRNA target interactions. RESULTS: A panel of eight, 23 and 27 miRNAs were associated with tumor size, LN, and REC status, respectively. Combined ROC analysis of two (miR-2117, and miR-378c), seven (let-7f-5p, miR-1255b-5p, miR-1268b, miR-200c-3p, miR-520d, miR-527, and miR-518a-5p), and three (miR-1200, miR-1249-3p, and miR-1271-3p) miRNAs showed a robust discriminatory power based on tumor size (AUC = 0.917), LN (AUC = 0.945) and REC (AUC = 0.981) status, respectively. Enrichment pathway analysis revealed their involvement in proteoglycans and glycan and cancer-associated pathways. Eight miRNAs with deregulated expressions in patients with large tumor size, positive LN metastasis, and recurrence were significantly associated with lower survival rates. Finally, the construction of miRNA/mRNA networks based in experimentally validated mRNA targets, revealed nodes of critical cancer genes, such as AKT1, BCL2, CDKN1A, EZR and PTEN. CONCLUSIONS: Altogether, our data indicate that miRNA deregulated expression is a relevant biological factor that can be associated with the poor prognosis in TNBC of AA patients, by conferring to their TNBC cells aggressive phenotypes that are reflected in the clinical characteristics evaluated in this study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08573-2. |
format | Online Article Text |
id | pubmed-8317413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83174132021-07-30 A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer Turkistani, Safaa Sugita, Bruna M. Fadda, Paolo Marchi, Rafael Afsari, Ali Naab, Tammey Apprey, Victor Copeland, Robert L. Campbell, Michael C. Cavalli, Luciane R. Kanaan, Yasmine BMC Cancer Research BACKGROUND: To investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC). METHODS: Twenty-five samples of AA TNBC patients were profiled for global miRNA expression and stratified considering three clinical-pathological parameters: tumor size, lymph node (LN), and recurrence (REC) status. Differential miRNA expression analysis was performed for each parameter, and their discriminatory power was determined by Receiver Operating Characteristic (ROC) curve analysis. KMplotter was assessed to determine the association of the miRNAs with survival, and functional enrichment analysis to determine the main affected pathways and miRNA/mRNA target interactions. RESULTS: A panel of eight, 23 and 27 miRNAs were associated with tumor size, LN, and REC status, respectively. Combined ROC analysis of two (miR-2117, and miR-378c), seven (let-7f-5p, miR-1255b-5p, miR-1268b, miR-200c-3p, miR-520d, miR-527, and miR-518a-5p), and three (miR-1200, miR-1249-3p, and miR-1271-3p) miRNAs showed a robust discriminatory power based on tumor size (AUC = 0.917), LN (AUC = 0.945) and REC (AUC = 0.981) status, respectively. Enrichment pathway analysis revealed their involvement in proteoglycans and glycan and cancer-associated pathways. Eight miRNAs with deregulated expressions in patients with large tumor size, positive LN metastasis, and recurrence were significantly associated with lower survival rates. Finally, the construction of miRNA/mRNA networks based in experimentally validated mRNA targets, revealed nodes of critical cancer genes, such as AKT1, BCL2, CDKN1A, EZR and PTEN. CONCLUSIONS: Altogether, our data indicate that miRNA deregulated expression is a relevant biological factor that can be associated with the poor prognosis in TNBC of AA patients, by conferring to their TNBC cells aggressive phenotypes that are reflected in the clinical characteristics evaluated in this study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08573-2. BioMed Central 2021-07-27 /pmc/articles/PMC8317413/ /pubmed/34315420 http://dx.doi.org/10.1186/s12885-021-08573-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Turkistani, Safaa Sugita, Bruna M. Fadda, Paolo Marchi, Rafael Afsari, Ali Naab, Tammey Apprey, Victor Copeland, Robert L. Campbell, Michael C. Cavalli, Luciane R. Kanaan, Yasmine A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer |
title | A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer |
title_full | A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer |
title_fullStr | A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer |
title_full_unstemmed | A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer |
title_short | A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer |
title_sort | panel of mirnas as prognostic markers for african-american patients with triple negative breast cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317413/ https://www.ncbi.nlm.nih.gov/pubmed/34315420 http://dx.doi.org/10.1186/s12885-021-08573-2 |
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