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

Cancer Cell International

Research

Mona S. Abdellateif¹  Ibrahim Malash²  Magda Mourad³  Abeer Bahnassy³  Abdel-Rahman N. Zekri⁴  Ola Ahmed⁴ 

[1] Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt;Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt;Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt;Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt;

关键词: Stem cells;    Breast cancer;    CD44;    CD24;    EpCAM;    NOTCH;   

DOI  :  10.1186/s12935-022-02841-2

 received in 2022-11-18, accepted in 2022-12-24,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundBreast 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.MethodsFresh 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.ResultsThe 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.ConclusionBCSCs have specific molecular profiles that differ according to their phenotypes which could affect patients’ prognosis and outcome.

【 授权许可】

CC BY   
© The Author(s) 2022

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