Expression of estrogen receptors and androgen receptor and their clinical significance in gastric cancer

// Wenbo Tang 1, 2, * , Rujiao Liu 1, 2, * , Yan Yan 1, 2, * , Xiaoli Pan 3 , Minjun Wang 4 , Xiaotian Han 2, 5 , Hui Ren 6 and Zhe Zhang 1, 2 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China 3 Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China 4 Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, P.R. China 5 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China 6 Department of Breast Surgery, Lanzhou General Hospital, Lanzhou, P.R. China * These authors have contributed equally to the work Correspondence to: Zhe Zhang, email: zhangzhe2010fduscc@gmail.com Keywords: gastric cancer, estrogen receptor, androgen receptor, epithelial-mesenchymal transition Received: April 04, 2016     Accepted: March 13, 2017     Published: March 28, 2017 ABSTRACT Despite the mounting studies exploring the role of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ) and androgen receptor (AR) in gastric cancer (GC), there remain controversies in those findings. The present study investigated the expression of ERα, ERβ and AR in Chinese gastric cancer by immunohistochemistry, analyzed their clinical relevance in gastric cancer, and examined the potential mechanisms by which ERα and AR modulated GC progression. The positive rate of ERα, ERβ and AR in GC tissues was 6% (9/150), 93.5% (143/153), and 42.4% (59/139), respectively. The expression of ERα was an independent unfavorable risk factor for overall survival (OS) (hazard ratio [HR] = 3.639, 95% confidence interval [CI] = 1.432-9.246, p = 0.007) for GC patients. Moreover, AR was borderline significantly associated with poor progress free survival (PFS) after adjustment with other variables (HR = 1.573, 95% CI = 0.955-2.592, p = 0.075). Knockdown of ERα inhibited the proliferation, migration and invasion of GC cells possibly via modulating the expression of p53, p21, p27, cyclin D1 and E-cadherin. Downregulation of AR suppressed the migration and invasion of GC cells and inhibited the epithelial-mesenchymal transition (EMT) associated pathways. Conclusion: The present study showed that positive ERα was associated with poor prognosis of Chinese GC patients. ERα might modulate the proliferation, migration and invasion via regulating the expression of p53, p21, p27, cyclin D1 and E-cadherin. ERα could be a valuable prognostic biomarker and promising therapeutic target for Chinese GC patients.