Abstract
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. 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. 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. 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.
Highlights
Oestrogen receptor (ER) is the driving transcription factor in up to three-quarters of all breast cancer (BC) and its protein expression by immunohistochemistry classifies patients as either having ER+ or ER-negative (ER–) disease
KIF18A protein expression is over expressed in BC compared with normal breast and it has been proposed as a useful predictive marker for lymph node metastasis [8]
We explore the possibility of KIF18A as a biomarker for the prognosis of ER+ BC patients and as a predictor of endocrine response
Summary
Oestrogen receptor (ER) is the driving transcription factor in up to three-quarters of all BC and its protein expression by immunohistochemistry classifies patients as either having ER+ or ER-negative (ER–) disease. It is desirable to be able to predict, at an early stage of treatment, which ER+ patients will benefit from endocrine therapy [2]. ER is a putative cargo for KIF18A, and presents a novel interaction between them that may have important physiological and pharmacological implications for oestrogen action in various cells [9, 10]. Both oestrogen and ER can up-regulate the expression of KIF18A mRNA and protein in vivo and in vitro suggesting that KIF18A may be associated with ER-related cancers [10]. We explore the possibility of KIF18A as a biomarker for the prognosis of ER+ BC patients and as a predictor of endocrine response
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