Characteristics and prognostic significance of polo‐like kinase‐1 (PLK1) expression in breast cancer

Author:

Lashen Ayat G123ORCID,Toss Michael S134ORCID,Wootton Louisa1,Green Andrew R.13ORCID,Mongan Nigel P56ORCID,Madhusudan Srinivasan17ORCID,Rakha Emad128ORCID

Affiliation:

1. Academic Unit for Translational Medical Sciences, School of Medicine University of Nottingham Nottingham UK

2. Department of Pathology, Faculty of Medicine Menoufia University Shebin El Kom Egypt

3. Nottingham Breast Cancer Research Centre University of Nottingham Nottingham UK

4. Department of Histopathology Sheffield Teaching Hospitals NHS Foundation Trust Sheffield Sheffield UK

5. School of Veterinary Medicine and Sciences University of Nottingham Nottingham UK

6. Department of Pharmacology Weill Cornell Medicine New York NY USA

7. Department of Oncology Nottingham University Hospitals Nottingham UK

8. Department of Pathology Hamad Medical Corporation Doha Qatar

Abstract

AimPolo‐like kinase‐1 (PLK1) plays a crucial role in cell cycle progression, and it is considered a potential therapeutic target in many cancers. Although the role of PLK1 is well established in triple‐negative breast cancer (TNBC) as an oncogene, its role in luminal BC is still controversial. In this study, we aimed to evaluate the prognostic and predictive role of PLK1 in BC and its molecular subtypes.MethodsA large BC cohort (n = 1208) were immunohistochemically stained for PLK1. The association with clinicopathological, molecular subtypes, and survival data was analysed. PLK1 mRNA was evaluated in the publicly available datasets (n = 6774), including The Cancer Genome Atlas and the Kaplan–Meier Plotter tool.Results20% of the study cohort showed high cytoplasmic PLK1 expression. High PLK1 expression was significantly associated with a better outcome in the whole cohort, luminal BC. In contrast, high PLK1 expression was associated with a poor outcome in TNBC. Multivariate analyses indicated that high PLK1 expression is independently associated with longer survival in luminal BC, and in poorer prognosis in TNBC. At the mRNA levels, PLK1 expression was associated with short survival in TNBC consistent with the protein expression. However, in luminal BC, its prognostic value significantly varies between cohorts.ConclusionThe prognostic role of PLK1 in BC is molecular subtype‐dependent. As PLK1 inhibitors are introduced to clinical trials for several cancer types, our study supports evaluation of the pharmacological inhibition of PLK1 as an attractive therapeutic target in TNBC. However, in luminal BC, PLK1 prognostic role remains controversial.

Publisher

Wiley

Subject

General Medicine,Histology,Pathology and Forensic Medicine

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