Lack of both androgen receptor and forkhead box A1 (FOXA1) expression is a poor prognostic factor in estrogen receptor-positive breast cancers
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Seho Park1,2,*, Eunjin Koh3,*, Ja Seung Koo4, Seung Il Kim1, Byeong-Woo Park1 and Kyung-Sup Kim3
1Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
2Frontier Research Institute of Convergence Sports Science, Yonsei University, Seoul, South Korea
3Department of Biochemistry and Molecular Biology, Institute for Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, South Korea
4Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
*These authors have contributed equally to this work
Seung Il Kim, email: [email protected]
Kyung-Sup Kim, email: [email protected]
Keywords: androgen receptor, breast neoplasms, estrogen receptor, forkhead box A1, prognosis
Received: February 02, 2017 Accepted: July 18, 2017 Published: September 15, 2017
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.
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