High AURKA expression in triple negative breast cancer correlates with expression of CIP2A and PME-1

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous breast cancer subtype which lacks expression of receptors usually targeted in breast cancer therapy. Thus, treatment options rely only on generalised chemotherapy, which carries cytotoxic consequences. Studies have shown that the tumour suppressor, protein phosphatase 2A (PP2A) was found to be deregulated in approximately 60% of TNBCs. The aims of the study are to evaluate protein expression of AURKA and KIF2C as biomarkers of interest in relation to PP2A activity in a cohort of TNBC patients, to identify biomarkers correlating with AURKA and KIF2C at RNA level, to confirm the selected biomarkers at protein level in the TNBC cohort, and in TNBC cell models following treatment with PP2A activator FTY720. Protein expression of AURKA and KIF2C was investigated in 160 TNBC cases and 23 normal breast epithelia by immunohistochemistry. Overexpression of these biomarkers was correlated with RNA profiles (40-gene panel, established in previous studies) assessed using a branched DNA assay to identify potential complimentary biomarkers related to AURKA and KIF2C expression. Protein expression of these biomarkers together with proliferation marker Ki67 was assessed on TNBC cell line models (N=6) treated with PP2A activator, FTY720 and on the TNBC patient cohort. 72% of TNBC patients overexpressed AURKA protein while 56% showed KIF2C protein expression. PP2A negative regulators CIP2A and PME-1 were found to be positively correlated with AURKA and KIF2C RNA and protein expression. No significant reduction was observed in TNBC cell lines following treatment FTY720. The AURKA, CIP2A and PME-1 biomarker signature identifies a potential therapeutic group within the TNBC cohort characterised by PP2A deregulation. Furthermore, inhibitors targeting these biomarkers should also be considered for evaluation in TNBC.