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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2018

01-08-2018 | Clinical trial

Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis

Authors: Sasagu Kurozumi, Chitra Joseph, Sultan Sonbul, Kylie L. Gorringe, Marian Pigera, Mohammed A. Aleskandarany, Maria Diez-Rodriguez, Christopher C. Nolan, Takaaki Fujii, Ken Shirabe, Hiroyuki Kuwano, Sarah Storr, Stewart G. Martin, Ian O. Ellis, Andrew R. Green, Emad A. Rakha

Published in: Breast Cancer Research and Treatment | Issue 3/2018

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Abstract

Background

The functions of many proteins are tightly regulated with a complex array of cellular functions including ubiquitination. In cancer cells, aberrant ubiquitination may promote the activity of oncogenic pathways with subsequent tumour progression. Kelch-like family member 7 (KLHL7) is involved in the regulation of ubiquitination and may play a role in breast cancer (BC). Present study aims to evaluate the biological and clinical usefulness of KLHL7 in BC utilising large well-characterised cohorts with long-term follow-up.

Methods

The relationships between KLHL7 gene copy number alteration (CNA) and mRNA expression and clinicopathological variables and clinical outcomes were evaluated in 1980 patients from the METABRIC BC cohort. Prognostic significance of KLHL7 mRNA was validated using the Breast Cancer Gene-Expression Miner v4.0 datasets (n = 5206). KLHL7 protein expression was assessed using immunohistochemistry in a large annotated series of early-stage BC (n = 917) with long-term follow-up.

Results

KLHL7 CNA was significantly correlated with its mRNA expression. KLHL7 mRNA expression was higher in luminal B and basal-like molecular subtypes and in higher grade tumours. Increased KLHL7 protein expression was significantly correlated with features of aggressive phenotype including lymphovascular invasion, high histological grade, hormonal receptor negativity, high PIK3CA and p53 expression. Outcome analysis showed that high KLHL7 expression is an independent predictor of shorter survival (p = 0.0011).

Conclusions

KLHL7 appears to play an important role in BC progression. High KLHL7 protein expression identified a subgroup of BC with aggressive behaviour and provided independent prognostic information.
Appendix
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Metadata
Title
Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis
Authors
Sasagu Kurozumi
Chitra Joseph
Sultan Sonbul
Kylie L. Gorringe
Marian Pigera
Mohammed A. Aleskandarany
Maria Diez-Rodriguez
Christopher C. Nolan
Takaaki Fujii
Ken Shirabe
Hiroyuki Kuwano
Sarah Storr
Stewart G. Martin
Ian O. Ellis
Andrew R. Green
Emad A. Rakha
Publication date
01-08-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4777-z

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