Research Paper Volume 11, Issue 18 pp 7442—7456

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

Xuan Jing 1, , Hongping Liang 1, , Chonghua Hao 1, , Li Hongxia 3, , Xiangrong Cui 2, ,

  • 1 Department of Clinical Laboratory, Shanxi Provincial People's Hospital, Affiliate of Shanxi Medical University, Taiyuan 030001, P.R. China
  • 2 Reproductive Medicine Center, Children's Hospital of Shanxi and Women Health Center of Shanxi, Affiliate of Shanxi Medical University, Taiyuan, Shanxi 030000, P.R. China
  • 3 Department of Oncology, Shanxi Provincial People's Hospital, Affiliate of Shanxi Medical University, Taiyuan 030001, P.R. China

received: May 20, 2019 ; accepted: September 2, 2019 ; published: September 28, 2019 ;

https://doi.org/10.18632/aging.102250
How to Cite

Copyright © 2019 Jing et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

BC: Breast Cancer; FOXA1: Forkhead box protein A1; HER-2: Human epidermal growth factor receptor-2; ER: Estrogen receptor; PR: Progesterone receptor; SAGE: Serial analysis of gene expression; GEPIA: Gene expression profiling interactive analysis; TCGA: The Cancer Genome Atlas; RFS: Recurrence-free survival; SBR: Scarff Bloom and Richardson.