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Lack of both androgen receptor and forkhead box A1 (FOXA1) expression is a poor prognostic factor in estrogen receptor-positive breast cancer

Authors
 Seho Park  ;  Eunjin Koh  ;  Ja Seung Koo  ;  Seung Il Kim  ;  Byeong-Woo Park  ;  Kyung-Sup Kim 
Citation
 Oncotarget, Vol.8(47) : 82940-82955, 2017 
Journal Title
 Oncotarget 
Issue Date
2017
Keywords
androgen receptor ; breast neoplasms ; estrogen receptor ; forkhead box A1 ; prognosis
Abstract
The present study aimed to examine the associations between androgen receptor (AR) and forkhead box A1 (FOXA1) and to investigate clinicopathological features and survival according to both biomarker status in estrogen receptor (ER)-positive breast cancers using in vitro study, patient cohort data, and the cBioPortal for Cancer Genomics and Kaplan-Meier Plotter websites. Experiments using T47D and ZR75-1 demonstrated AR-overexpressing cell lines decreased in cell proliferation through downregulation of ER, but FOXA1 did not change. Knockdown of FOXA1 resulted in a significantly reduced cell viability. Patients with immunohistochemically AR(-)/FOXA1(-) tumor frequently showed node metastasis, high grade, and high Ki-67 proliferation, therefore, significantly worse survival in ER-positive disease. AR and FOXA1 mRNA levels were significantly higher in ER-positive than in ER-negative tumors and AR-low/FOXA1-low tumors showed high grade, frequent basal-like subtype and worse disease-free survival in ER-positive cancers of public gene dataset, similarly to patient cohort results. The Kaplan-Meier Plotter analysis independently validated patients with both low AR/FOXA1 tumor were significantly associated with worse relapse-free survival in ER-positive cancers. This study suggests that distinctive clinicopathological features according to AR and FOXA1 are determined and a lack of both biomarkers is an independent poor prognostic factor in ER-positive tumors.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/161273
DOI
10.18632/oncotarget.20937
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
고은진(Koh, Eun Jin) ; 구자승(Koo, Ja Seung) ; 김경섭(Kim, Kyung Sup) ; 김승일(Kim, Seung Il) ; 박병우(Park, Byeong Woo) ; 박세호(Park, Se Ho)
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