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

  • Preclinical study
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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 < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 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.

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Abbreviations

BC:

Breast cancer

BCSS:

BC-specific survival

CI:

Confidence intervals

ER:

Oestrogen

HR:

Hazard ratio

HER2:

Human epidermal growth factor receptor 2

METABRIC:

Molecular taxonomy of breast cancer international consortium

NPI:

Nottingham Prognostic Index

PR:

Progesterone

TCGA:

The cancer genome atlas

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Acknowledgements

We thank the Nottingham Health Science Biobank and Breast Cancer Now Tissue Bank for the provision of tissue samples.

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Correspondence to Emad A. Rakha.

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This study was approved by the Nottingham Research Ethics Committee 2 (Reference title: Development of a molecular genetic classification of breast cancer). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Joseph, C., Arshad, M., Kurozomi, S. et al. Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer. Breast Cancer Res Treat 174, 387–399 (2019). https://doi.org/10.1007/s10549-018-05085-9

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