MA Aleskandarany, OH Negm, EA Rakha, MAH Ahmed, CC Nolan, GR Ball, C Caldas, AR Green, PJ Tighe, IO Ellis
Breast Cancer Res Treat
Appropriate mitochondrial functioning in normal cells depends on proper functioning of mitochondrial translocation machinery, of which translocase of the outer membrane of mitochondria (TOMM) plays important role. The aim of this study was to explore the expression of TOMM34 in invasive breast cancer (BC) with relevance to BC molecular subtypes and patients' outcome. Gene expression data of 128 BC were analysed using artificial neuronal network (ANN) analysis to identify differentially expressed genes between BC with distant metastases and that without distant metastases. TOMM34 expression was assessed in a large series of BC (n = 1,061) with long-term follow-up using tissue microarray and immunohistochemistry. TOMM34 protein expression was quantitatively measured using the novel reverse phase protein microarray (RPPA) technique. ANN analysis revealed TOMM34 gene transcript as one of the top differentially expressed gene correlated with BC distant metastasis. Protein expression of TOMM34 was associated with features of aggressive behaviour including higher tumour grade, advanced nodal stage, larger tumour size and lymphovascular invasion. TOMM34 over-expression was significantly associated with shorter BC-specific survival and metastasis-free survival independent of standard prognostic parameters. TOMM34 protein expression was quantified by RPPA which showed that the mean expression values of TOMM34 were higher in samples demonstrating features of poor outcome. This study demonstrates at translational protein expression level that TOMM34 is a marker of poor prognosis in BC. Our findings underscore the role played by mitochondrial machinery in BC progression and warrant their validation on a prospective basis.