Analyses of an epigenetic switch involved in the activation of pioneer factor FOXA1 leading to the prognostic value of estrogen receptor and FOXA1 co-expression in breast cancer

Abstract

Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor α (ER)–chromatin binding and function, yet the role of FOXA1 in breast cancer and the underlying molecular mechanisms have not yet been elucidated. To evaluate gene expression alterations during breast carcinogenesis, FOXA1 expression was analyzed using the Serial Analysis of Gene Expression Genie suite, a gene expression profiling interactive analysis, and Oncomine analyses. The correlation between methylation and expression was analyzed using the MEXPRESS tool and UCSC Xena browser. Then, the expression and prognostic value of FOXA1 was validated by our own breast cancer samples using RT-PCR. We obtained the following important results. (1) The expression level of FOXA1 was significantly higher in breast cancer than normal tissues. (2) ER, PR, HEGR-2, and nodal status were positively correlated with FOXA1 expression. (3) Among patients with ER+ tumors, those with higher FOXA1 expression levels had better survival probabilities. (4) The major mutation type in FOXA1 in breast cancer samples was missense mutations. (5) FOXA1 expression was significantly higher in ER+ breast tumors than in ER− tumors or normal tissues. Our findings suggest that the aberrant DNA hypomethylation of promoter regions is one mechanism underlying the aberrant expression of FOXA1 in ER+ breast cancer, which might be a potential indicator of favorable prognosis.