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.
Highlights
Breast cancer is the most frequent cancer in women worldwide and the fifth leading cancer-related cause of death, with about 1.7 million cases diagnosed and about 0.5 million associated deaths globally in 2011 according to the World Health Organization [1]
Our findings suggest that the aberrant DNA hypomethylation of promoter regions is one mechanism underlying the aberrant expression of Forkhead box protein A1 (FOXA1) in estrogen receptor α (ER)+ breast cancer, which might be a potential indicator of favorable prognosis
Using Gene expression profiling interactive analysis (GEPIA), we found that the expression level of FOXA1 was significantly higher in breast cancer, cervical squamous cell carcinoma, endocervical adenocarcinoma, colon adenocarcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, rectum adenocarcinoma, uterine corpus endometrial carcinoma, and uterine carcinosarcoma than in their matched normal tissues (Figure 2)
Summary
Breast cancer is the most frequent cancer in women worldwide and the fifth leading cancer-related cause of death, with about 1.7 million cases diagnosed and about 0.5 million associated deaths globally in 2011 according to the World Health Organization [1]. Several clinicopathological features, such as tumor size, histological subtype and grade, lymph node metastases, hormone receptor status, and the expression of human epidermal growth factor receptor-2 (HER-2), have been implemented in breast cancer management [2]. Understanding why and how ER+ breast cancers differ is important from research and clinical perspectives
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
