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Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+ breast cancer

  • Lutfi H. Alfarsi
  • Rokaya Elansari
  • Michael S. Toss
  • Maria Diez-Rodriguez
  • Christopher C. Nolan
  • Ian O. Ellis
  • Emad A. Rakha
  • Andrew R. Green
Preclinical study
  • 66 Downloads

Abstract

Purpose

Identification of effective and reliable biomarkers that could be used to predict the efficacy of endocrine therapy is of crucial importance to the management of oestrogen receptor positive (ER+) breast cancer (BC). KIF18A, a key regulator of cell cycle, is overexpressed in many human cancers, including BC. In this study, we investigated the role of KIF18A as a biomarker to predict the benefit from endocrine treatment in early ER + BC patients.

Methods

KIF18A expression was assessed at the genomic level using the METABRIC dataset to explore its prognostic and predictive value in ER + BC patients (n = 1506). Predictive significance of KIF18A mRNA was validated using KM-Plot datasets (n = 2061). KIF18A protein expression was assessed using immunohistochemistry in a large annotated series of early-stage ER + BC (n = 1592) with long-term follow-up.

Results

High mRNA and protein expression of KIF18A were associated with short recurrence-free survival (RFS), distant-metastasis free survival (DMFS) and BC specific survival (all P < 0.05) in ER + BC in patients who received no adjuvant treatment or adjuvant endocrine therapy. In multivariate analysis, high KIF18A expression was an independent prognostic biomarker for poor RFS (P = 0.027) and DMFS (P = 0.028) in patients treated with adjuvant endocrine therapy.

Conclusion

KIF18A appears to be a candidate biomarker of a subgroup of ER + BC characterised by poor clinical outcome. High KIF18A expression has prognostic significance to predict poor benefit from endocrine treatment for patients with ER + BC. Therefore, measurement of KIF18A on ER + BC patients prior to treatment could guide clinician decision on benefit from endocrine therapy.

Keywords

Breast cancer Oestrogen receptor Endocrine treatment Predictive biomarker KIF18A 

Notes

Acknowledgements

We thank the Nottingham Health Science Biobank and Breast Cancer Now Tissue Bank for the provision of tissue samples. We thank the University of Nottingham (Nottingham Life Cycle 6 and Cancer Research Priority Area) and Saudi Arabia Cultural Embassy for funding.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

This study was approved by the Nottingham Research Ethics Committee 2 under the title “Development of a molecular genetic classification of breast cancer”.

Supplementary material

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Supplementary material 1 (TIF 4896 KB)
10549_2018_4978_MOESM2_ESM.tif (7.3 mb)
Supplementary material 2 (TIF 7424 KB)

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Copyright information

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

Authors and Affiliations

  • Lutfi H. Alfarsi
    • 1
  • Rokaya Elansari
    • 1
  • Michael S. Toss
    • 1
  • Maria Diez-Rodriguez
    • 1
  • Christopher C. Nolan
    • 1
  • Ian O. Ellis
    • 1
    • 2
  • Emad A. Rakha
    • 1
    • 2
  • Andrew R. Green
    • 1
  1. 1.Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Nottingham City HospitalUniversity of NottinghamNottinghamUK
  2. 2.Cellular PathologyNottingham University Hospitals NHS TrustNottinghamUK

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