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

  • Chitra Joseph
  • Maariya Arshad
  • Sasagu Kurozomi
  • Maryam Althobiti
  • Islam M. Miligy
  • Sara Al-izzi
  • Michael S. Toss
  • Fang Qin Goh
  • Simon J. Johnston
  • Stewart G. Martin
  • Ian O. Ellis
  • Nigel P. Mongan
  • Andrew R. Green
  • Emad A. RakhaEmail author
Preclinical study
  • 157 Downloads

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.

Keywords

Cancer Stem Cell Invasive breast cancer Prognosis CD133 

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

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Research involving human participants

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10549_2018_5085_MOESM1_ESM.pdf (360 kb)
Supplementary material 1 (PDF 360 KB)
10549_2018_5085_MOESM2_ESM.docx (17 kb)
Supplementary material 2 (DOCX 17 KB)
10549_2018_5085_MOESM3_ESM.docx (15 kb)
Supplementary material 3 (DOCX 15 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Chitra Joseph
    • 1
  • Maariya Arshad
    • 1
  • Sasagu Kurozomi
    • 1
    • 2
  • Maryam Althobiti
    • 1
  • Islam M. Miligy
    • 1
    • 5
  • Sara Al-izzi
    • 1
  • Michael S. Toss
    • 1
    • 5
  • Fang Qin Goh
    • 1
  • Simon J. Johnston
    • 1
  • Stewart G. Martin
    • 1
  • Ian O. Ellis
    • 1
    • 6
  • Nigel P. Mongan
    • 3
    • 4
  • Andrew R. Green
    • 1
  • Emad A. Rakha
    • 1
    • 5
    • 6
    Email author
  1. 1.Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of MedicineUniversity of NottinghamNottinghamUK
  2. 2.Department of General Surgical ScienceGunma University Graduate School of MedicineGunmaJapan
  3. 3.Cancer Biology and Translational Research, Faculty of Medicine and Health SciencesUniversity of NottinghamNottinghamUK
  4. 4.Department of PharmacologyWeill Cornell MedicineNew YorkUSA
  5. 5.Histopathology Department, Faculty of MedicineMenoufia UniversityShebin El-komEgypt
  6. 6.Department of Histopathology, School of MedicineNottingham University Hospitals NHS Trust, Nottingham City HospitalNottinghamUK

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