الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer stem cells (BCSCs) are a small subset of cells that are responsible for initiation and propagation of breast cancer. These BCSCs have certain stem cell-like properties, such as, self-renewal and multi-potential differentiation, thus, driving tumorigenesis, recurrence and growth at metastatic sites. The cancer stem-cell like behavior is associated with metastatic potential, in particular the ability to seed new tumour foci to distant sites. BCSCs are also more resistant to systemic chemotherapy and radiotherapy than the bulk tumour cells and thus are believed to be responsible for tumour recurrences.
Unfortunately, the molecular signature of BCSCs, particularly from human primary cancers, remains poorly defined. The improved knowledge concerning the exact characteristics of BCSCs will aid design of novel therapies targeting BCSCs to reduce metastatic recurrences and thereby improve outcomes.
In this study, 17 patients with primary breast cancer were recruited, including those with a range of histopathological and molecular subtypes. BCSCs were fluorescently labelled based on their functional ALDH activity using the Aldefluor assay and isolated by cell sorting (FACS). The proportion of Aldefluor positive cancer cells (BCSCs) varied from 0 to 9.4% (mean 3.8%).
The transcriptomic profile of BCSCs, and for comparison, the matched bulk cancer cells were determined using RNA-sequencing from 6 breast cancer cases. The expression profiles were compared in order to define consistent characteristics of BCSCs.
Unsupervised hierarchical clustering of expression profiles showed that samples clustered mainly pairwise (BCSCs with their matched non-stem cells), demonstrating that differences between the diverse cases included in this cohort were overall greater than paired differences between stem and non-stem compartments.
The transcriptomes were analysed to identify significantly differentially expressed transcripts between BCSCs and bulk breast cancer cells, using all 6 sample pairs, or only 5 sample pairs. After robust correction for multiple testing, 55 differentially expressed transcripts were identified using all 6 sample pairs (54 down-regulated in BCSCs, and only 1 up-regulated) and 130 transcripts were identified using the 5 sample pairs (118 down-regulated and 12 up-regulated).
The differentially expressed transcripts were resolved into lists of differentially expressed genes. 38 differentially expressed genes were identified using all 6 sample pairs (37 down-regulated in BCSCs, and only 1 up-regulated) and 88 genes were identified using the 5 sample pairs (80 down-regulated and 8 up-regulated).
The most up-regulated gene in BCSCs was PDGFRA, while the most down-regulated was HBB. Overall, the differentially expressed genes were significantly enriched for functions in vessel morphogenesis, cell motility, and metabolism.