Identification of candidate genes that may function in ER- breast cancer

Abstract

Breast cancer is the most common cancer in women worldwide. Most breast cancers are hormone related involving the oestrogen receptor (ER), progesterone receptor (PR) and/or the human epidermal growth factor (HER2). The majority of aggressive (invasive and metastatic) breast cancers are negative for the ER receptor (ER-) including the triple negative and basal subtypes (ER-, PR-, HER2-). Due to this, traditional treatments such as hormonal replacement therapy are not suitable. Using bioinformatics, R scripting, and datasets from 1,485 Caucasian samples (1,437 tumours and 48 normal tissues) with 21,000 genes from the publicly available online GEO database (NCBI), we compared expression levels of ER negative (ER-) tumours to ER positive (ER+) tumours. 7 protein coding genes were identified as candidate functional genes, where their expression was significantly up-regulated in ER- tumours (log2 FC= 1.02-1.24, P=2.98E-31 - 6.47E-19) which correlated with reduced survival using distant metastasis free survival (DMFS) in Kaplan-Meier plotter (Log rank test, P=0.0013-0.033). Next, we will determine the effect of copy number changes, the functions of the genes in triple negative breast cancers and in cellular pathways, and then validate these results in the laboratory to test their potential as novel therapeutic targets in aggressive cancers and as biomarkers to predict prognosis or metastases