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

Autor: Alfarsi, Lutfi H., Elansari, Rokaya, Toss, Michael S., Diez-Rodriguez, Maria, Nolan, Christopher C., Ellis, Ian O., Rakha, Emad A., Green, Andrew R.
Jazyk: angličtina
Rok vydání: 2018
Předmět:
ISSN: 0167-6806
1573-7217
Popis: 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? less than 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.
Databáze: OpenAIRE
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