Rho-GTPase activating-protein 18: A biomarker associated with good prognosis in invasive breast cancer

Aleskandarany, Mohammed A.; Sonbul, Sultan N.; Surridge, Rachel; Mukherjee, Abhik; Caldas, Carlos; Diez-Rodriguez, Maria; Ashankyty, Ibraheem; Albrahim, Khalil I.; Elmouna, Ahmed M.; Aneja, Ritu; Martin, Stewart G.; Ellis, Ian O.; Green, Andrew R.; Rakha, Emad A.

Abstract

© 2017 Cancer Research UK. All rights reserved. Background:The prognostic value of lymphovascular invasion (LVI) in breast cancer (BC) has been demonstrated in several independent studies. However, identification of driver molecules for LVI remains a challenging task. Large-scale transcriptomic profiling of histologically validated LVI can potentially identify genes that regulate LVI.Methods:Integrative bio-informatics analyses of the METABRIC study were performed utilising a subset of strictly defined LVI using histological and immunohistochemical (IHC) criteria. ARHGAP18 was among the top differentially expressed genes between LVI+ and LVIa ' BC with a 1.8-fold change. The prognostic impact of ARHGAP18 gene expression was assessed in the METABRIC data set (n=1980) and externally validated using the online BC gene expression data sets utilising bc-GenExMiner v4.0 (n=2016). Subsequently, ARHGAP18 protein expression was assessed on a large cohort of invasive BC (n=959) with long-term follow-up using IHC.Results:Pooled analysis of ARHGAP18 mRNA expression showed that overexpression was associated with better outcome (P

• Journal Article Type: Article
• Acceptance Date: Jul 14, 2017
• Online Publication Date: Aug 22, 2017
• Publication Date: Aug 22, 2017
• Deposit Date: Jul 20, 2017
• Publicly Available Date: Aug 22, 2017
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 117
• Issue: 8
• Pages: 1176-1184
• DOI: https://doi.org/10.1038/bjc.2017.261
• Keywords: ARHGAP18, Lymphovascular invasion, Immunohistochemistry, Breast cancer, Prognosis
• Public URL: https://nottingham-repository.worktribe.com/output/878336
• Publisher URL: http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2017261a.html?foxtrotcallback=true