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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.

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


Authors

Maariya Arshad

Sasagu Kurozomi

Maryam Althobiti

Islam M. Miligy

Sara Al-Izzi

Michael S. Toss

Fang Qin Goh

Simon J. Johnston

STEWART MARTIN STEWART.MARTIN@NOTTINGHAM.AC.UK
Professor of Cancer and Radiation Biology

NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Professor of Oncology

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



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.

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