Ojiegbe, S., Joseph, C., Provenzano, E., Caldas, C., Nolan, C., Green, A.R., Rakha, E., 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.
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: |
12 Oct 2017 23:02 |
| URI: |
https://eprints.nottingham.ac.uk/id/eprint/43996 |
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