Transcriptome profiles of stem-like cells from primary breast cancers allow identification of ITGA7 as a predictive marker of chemotherapy response
Autor: | Waleed S. Al Amri, William E. Hughes, James L. Thorne, Geoff Wells, Ian M. Carr, Brian V Hogan, Thomas A. Hughes, Fiona Langlands, Arindam Pramanik, Layla K. Younis, Stacey J. Jones, Sarah A. Harris, Eldo T. Verghese, Rebecca Millican-Slater, Nevine M.F. El Deeb, Mervat A. Hamza, Baek Kim, Noha Gwili |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Cell Survival Down-Regulation Breast Neoplasms Biology Article Transcriptome 03 medical and health sciences Breast cancer 0302 clinical medicine Downregulation and upregulation Antigens CD Cell Line Tumor Biomarkers Tumor medicine Chemotherapy Humans Gene Cell Proliferation Predictive marker Cancer stem cells Sequence Analysis RNA Gene Expression Profiling medicine.disease Survival Analysis 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell MCF-7 Cells Neoplastic Stem Cells Cancer research Immunohistochemistry Female Stem cell Integrin alpha Chains |
Zdroj: | British Journal of Cancer |
ISSN: | 0007-0920 |
Popis: | Background Breast cancer stem cells (BCSCs) are drivers of therapy-resistance, therefore are responsible for poor survival. Molecular signatures of BCSCs from primary cancers remain undefined. Here, we identify the consistent transcriptome of primary BCSCs shared across breast cancer subtypes, and we examine the clinical relevance of ITGA7, one of the genes differentially expressed in BCSCs. Methods Primary BCSCs were assessed using immunohistochemistry and fluorescently labelled using Aldefluor (n = 17). Transcriptomes of fluorescently sorted BCSCs and matched non-stem cancer cells were determined using RNA-seq (n = 6). ITGA7 expression was examined in breast cancers using immunohistochemistry (n = 305), and its functional role was tested using siRNA in breast cancer cells. Results Proportions of BCSCs varied from 0 to 9.4%. 38 genes were significantly differentially expressed in BCSCs; genes were enriched for functions in vessel morphogenesis, motility, and metabolism. ITGA7 was found to be significantly downregulated in BCSCs, and low expression significantly correlated with reduced survival in patients treated with chemotherapy, and with chemoresistance in breast cancer cells in vitro. Conclusions This study is the first to define the molecular profile of BCSCs from a range of primary breast cancers. ITGA7 acts as a predictive marker for chemotherapy response, in accordance with its downregulation in BCSCs. |
Databáze: | OpenAIRE |
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