Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer

Joseph, Chitra; Arshad, Maariya; Kurozomi, Sasagu; Althobiti, Maryam; Miligy, Islam M.; Al-Izzi, Sara; Toss, Michael S.; Goh, Fang Qin; Johnston, Simon J.; Martin, Stewart G.; Ellis, Ian O.; Mongan, Nigel P.; Green, Andrew R.; Rakha, Emad A.

Abstract

Purpose
CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC.

Methods
CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated.

Results
High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p less than 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038).

Conclusion
This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.

Citation

Joseph, C., Arshad, M., Kurozomi, S., Althobiti, M., Miligy, I. M., Al-Izzi, S., …Rakha, E. A. (2019). Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer. Breast Cancer Research and Treatment, 174(2), 387-399. https://doi.org/10.1007/s10549-018-05085-9

• Journal Article Type: Article
• Acceptance Date: Dec 3, 2018
• Online Publication Date: Dec 15, 2018
• Publication Date: Apr 1, 2019
• Deposit Date: Dec 11, 2018
• Publicly Available Date: Dec 16, 2019
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 174
• Issue: 2
• Pages: 387-399
• DOI: https://doi.org/10.1007/s10549-018-05085-9
• Keywords: Cancer Stem Cell; invasive breast cancer; prognosis; CD133
• Public URL: https://nottingham-repository.worktribe.com/output/1405901
• Publisher URL: https://link.springer.com/article/10.1007/s10549-018-05085-9
• Contract Date: Dec 11, 2018