Elevated expression of STK3 mRNA and protein is associated with poor outcome in invasive breast cancer

Ojiegbe, S. and Joseph, C. and Provenzano, E. and Caldas, C. and Nolan, C. and Green, A.R. and Rakha, E. and Ellis, I.O. and Mukherjee, A. (2017) Elevated expression of STK3 mRNA and protein is associated with poor outcome in invasive breast cancer. In: Belfast Pathology 2017: 10th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 20-23 June 2017, Belfast, United Kingdom.

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Abstract

Purpose of the study: The mammalian sterile 20-like kinase (MST2/STK3) and its close homologue MST1(STK4) are members of the germinal centre kinase group II (GCK II) family of mitogen-activated protein kinases (MAPK). High STK3 expression is known to be correlated with poor prognosis in various cancers playing a role in cell migration and invasion. This study aimed to determine correlations of STK3 expression with clinicopathological variables in BCs.

Methods: STK3 mRNA expression was investigated in the METABRIC BC cohort (n=1980) and externally validated using online BC expression datasets [bc-GenExMiner v4.0]. STK3 protein expression was studied in a well characterised series of primary invasive BCs (n=1024) using immunohistochemistry including correlations with clinicopathological parameters, other biomarkers and patient outcome.

Results: Copy number (CN) gain of STK3 was correlated with adverse prognostic features: higher grade and poor NPI (p<0.0001) High STK3 expression was also associated with poor prognostic factors, including high grade, younger age, larger tumour size, poorer NPI and negative ER/PR status (p<0.001). In PAM50 subtypes, high STK3 expression was associated with Luminal B/basal like tumours. Cytoplasmic STK3(c-STK3) protein expression was associated with increased mitotic index, poorer NPI (p<0.001) and basal-like markers CK5/6 and EGFR (p<0.05). In univariate analysis, high c-STK3 expression showed poorer outcome in the whole cohort and ER+ subgroups (p<0.05). Pooled STK3 gene expression data in the external validation cohort confirmed association with poor outcome (p<0.0001, HR = 1.60, 95% CI 1.28–2.01).

Conclusions: Results suggest c-STK3 as a poor prognostic marker in invasive BC including ER+ subgroups warranting further functional studies.

Item Type: Conference or Workshop Item (Paper)
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Depositing User: Mukherjee, Abhik
Date Deposited: 07 Jul 2017 08:49
Last Modified: 09 Jul 2017 04:18
URI: http://eprints.nottingham.ac.uk/id/eprint/43996

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