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Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients

BACKGROUND: Breast cancer stem cells (BCSCs) have a crucial role in breast carcinogenesis, development, and progression. The aim of the current study is to characterize the BCSCs through the genetic profiling of different BCSCs phenotypic subsets to determine their related genetic pathways. METHODS:...

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Autores principales: Zekri, Abdel-Rahman N., Bahnassy, Abeer, Mourad, Magda, Malash, Ibrahim, Ahmed, Ola, Abdellateif, Mona S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9805169/
https://www.ncbi.nlm.nih.gov/pubmed/36585652
http://dx.doi.org/10.1186/s12935-022-02841-2
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author Zekri, Abdel-Rahman N.
Bahnassy, Abeer
Mourad, Magda
Malash, Ibrahim
Ahmed, Ola
Abdellateif, Mona S.
author_facet Zekri, Abdel-Rahman N.
Bahnassy, Abeer
Mourad, Magda
Malash, Ibrahim
Ahmed, Ola
Abdellateif, Mona S.
author_sort Zekri, Abdel-Rahman N.
collection PubMed
description BACKGROUND: Breast cancer stem cells (BCSCs) have a crucial role in breast carcinogenesis, development, and progression. The aim of the current study is to characterize the BCSCs through the genetic profiling of different BCSCs phenotypic subsets to determine their related genetic pathways. METHODS: Fresh tumor tissue samples were obtained from 31 breast cancer (BC) patients for (1) Mammosphere culture. (2) Magnetic separation of the BCSCs subsets using CD24, CD44, and CD326 Microbeads. (3) Flow cytometry (FCM) assay using CD44, CD24, and EpCAM. (4) RT-PCR profiler Arrays using stem cell (SC) panel of 84 genes for four group of cells (1) CD44(+)/CD24(−)/EpCAM(−) BCSCs, (2) CD44(+)/CD24(−) /EpCAM(+) BCSCs, (3) mammospheres, and (4) normal breast tissues. RESULTS: The BCSCs (CD44(+)/CD24(−)/EpCAM(−)) showed significant downregulation in 13 genes and upregulation in 15, where the CD44, GJB1 and GDF3 showed the maximal expression (P = 0.001, P = 0.003 and P = 0.007); respectively). The CD44(+)/CD24(−)/EpCAM(+) BCSCs showed significant upregulation in 28 genes, where the CD44, GDF3, and GJB1 showed maximal expression (P < 0.001, P = 0.001 and P = 0.003; respectively). The mammospheres showed significant downregulation in 9 genes and a significant upregulation in 35 genes. The maximal overexpression was observed in GJB1 and FGF2 (P = 0.001, P = 0.001; respectively). The genes which achieved significant overexpression in all SC subsets were CD44, COL9A1, FGF1, FGF2, GDF3, GJA1, GJB1, GJB2, HSPA9, and KRT15. While significant downregulation in BMP2, BMP3, EP300, and KAT8. The genes which were differentially expressed by the mammospheres compared to the other BCSC subsets were CCND2, FGF3, CD4, WNT1, KAT2A, NUMB, ACAN, COL2A1, TUBB3, ASCL2, FOXA2, ISL1, DTX1, and DVL1. CONCLUSION: BCSCs have specific molecular profiles that differ according to their phenotypes which could affect patients’ prognosis and outcome.
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spelling pubmed-98051692023-01-01 Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients Zekri, Abdel-Rahman N. Bahnassy, Abeer Mourad, Magda Malash, Ibrahim Ahmed, Ola Abdellateif, Mona S. Cancer Cell Int Research BACKGROUND: Breast cancer stem cells (BCSCs) have a crucial role in breast carcinogenesis, development, and progression. The aim of the current study is to characterize the BCSCs through the genetic profiling of different BCSCs phenotypic subsets to determine their related genetic pathways. METHODS: Fresh tumor tissue samples were obtained from 31 breast cancer (BC) patients for (1) Mammosphere culture. (2) Magnetic separation of the BCSCs subsets using CD24, CD44, and CD326 Microbeads. (3) Flow cytometry (FCM) assay using CD44, CD24, and EpCAM. (4) RT-PCR profiler Arrays using stem cell (SC) panel of 84 genes for four group of cells (1) CD44(+)/CD24(−)/EpCAM(−) BCSCs, (2) CD44(+)/CD24(−) /EpCAM(+) BCSCs, (3) mammospheres, and (4) normal breast tissues. RESULTS: The BCSCs (CD44(+)/CD24(−)/EpCAM(−)) showed significant downregulation in 13 genes and upregulation in 15, where the CD44, GJB1 and GDF3 showed the maximal expression (P = 0.001, P = 0.003 and P = 0.007); respectively). The CD44(+)/CD24(−)/EpCAM(+) BCSCs showed significant upregulation in 28 genes, where the CD44, GDF3, and GJB1 showed maximal expression (P < 0.001, P = 0.001 and P = 0.003; respectively). The mammospheres showed significant downregulation in 9 genes and a significant upregulation in 35 genes. The maximal overexpression was observed in GJB1 and FGF2 (P = 0.001, P = 0.001; respectively). The genes which achieved significant overexpression in all SC subsets were CD44, COL9A1, FGF1, FGF2, GDF3, GJA1, GJB1, GJB2, HSPA9, and KRT15. While significant downregulation in BMP2, BMP3, EP300, and KAT8. The genes which were differentially expressed by the mammospheres compared to the other BCSC subsets were CCND2, FGF3, CD4, WNT1, KAT2A, NUMB, ACAN, COL2A1, TUBB3, ASCL2, FOXA2, ISL1, DTX1, and DVL1. CONCLUSION: BCSCs have specific molecular profiles that differ according to their phenotypes which could affect patients’ prognosis and outcome. BioMed Central 2022-12-31 /pmc/articles/PMC9805169/ /pubmed/36585652 http://dx.doi.org/10.1186/s12935-022-02841-2 Text en © The Author(s) 2022 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
Zekri, Abdel-Rahman N.
Bahnassy, Abeer
Mourad, Magda
Malash, Ibrahim
Ahmed, Ola
Abdellateif, Mona S.
Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients
title Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients
title_full Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients
title_fullStr Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients
title_full_unstemmed Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients
title_short Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients
title_sort genetic profiling of different phenotypic subsets of breast cancer stem cells (bcscs) in breast cancer patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9805169/
https://www.ncbi.nlm.nih.gov/pubmed/36585652
http://dx.doi.org/10.1186/s12935-022-02841-2
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