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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
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.
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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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