乳腺癌患者中乳腺癌干细胞（BCSCs）不同表型亚群的基因谱分析。

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

作者信息

Zekri Abdel-Rahman N, Bahnassy Abeer, Mourad Magda, Malash Ibrahim, Ahmed Ola, Abdellateif Mona S

机构信息

Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Cancer Cell Int. 2022 Dec 31;22(1):423. doi: 10.1186/s12935-022-02841-2.

DOI:10.1186/s12935-022-02841-2

PMID:36585652

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9805169/

Abstract

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.

摘要

背景

乳腺癌干细胞（BCSCs）在乳腺癌的发生、发展和进展中起着关键作用。本研究的目的是通过对不同BCSCs表型亚群进行基因分析来表征BCSCs，以确定其相关的遗传途径。

方法

从31例乳腺癌（BC）患者中获取新鲜肿瘤组织样本，用于（1）乳腺球培养。（2）使用CD24、CD44和CD326微珠对BCSCs亚群进行磁性分离。（3）使用CD44、CD24和EpCAM进行流式细胞术（FCM）检测。（4）对四组细胞（1）CD44/CD24/EpCAM BCSCs、（2）CD44/CD24 /EpCAM BCSCs、（3）乳腺球和（4）正常乳腺组织，使用包含84个基因的干细胞（SC）面板进行RT-PCR分析阵列。

结果

BCSCs（CD44/CD24/EpCAM）在13个基因中显著下调，在15个基因中上调，其中CD44、GJB1和GDF3表达最高（分别为P = 0.001、P = 0.003和P = 0.007）；CD44/CD24/EpCAM BCSCs在28个基因中显著上调，其中CD44、GDF3和GJB1表达最高（分别为P < 0.001、P = 0.001和P = 0.003）。乳腺球在9个基因中显著下调，在35个基因中显著上调。GJB1和FGF2的过表达最为显著（分别为P = 0.001、P = 0.001）。在所有SC亚群中均实现显著过表达的基因有CD44、COL9A1、FGF1、FGF2、GDF3、GJA1、GJB1、GJB2、HSPA9和KRT15。而BMP2、BMP3、EP300和KAT8显著下调。与其他BCSC亚群相比，乳腺球差异表达的基因有CCND2、FGF3、CD4、WNT1、KAT2A、NUMB、ACAN、COL2A1、TUBB3、ASCL2、FOXA2、ISL1、DTX1和DVL1。