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Double-edged role of G protein-coupled estrogen receptor 1 in breast cancer prognosis: an analysis of 167 breast cancer samples and online data sets

Authors Yang F, Shao ZM

Received 2 May 2016

Accepted for publication 23 August 2016

Published 25 October 2016 Volume 2016:9 Pages 6407—6415


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jia Fan

Peer reviewer comments 3

Editor who approved publication: Professor Min Li

Fan Yang,1,2 Zhi-Min Shao1,2

1Department of Breast Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

Abstract: G protein-coupled estrogen receptor 1 (GPER1) is widely expressed in breast ­cancer; however, its prognostic significance in breast cancer patients remains controversial. In this study, expression levels of GPER1 were analyzed by using real-time polymerase chain reaction in 167 primary breast cancer samples, and overall survival (OS), recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were analyzed by using Kaplan–Meier curves and multivariable Cox regression. In addition, a meta-analysis was conducted with all available online data sets found in the Web sites and The results showed that there was no significant correlation between GPER1 expression and OS, RFS, DMFS, and DFS in the total breast cancer patient population. In contrast, the meta-analysis of online data sets found that expression levels of GPER1 were slightly associated with better RFS in the total breast cancer population (P=0.021). Interestingly, higher expression of GPER1 was associated with poorer DFS in HER2-positive subtype of breast cancer (P=0.047) but with better DMFS (P=0.040) and DFS (P=0.035) in HER2-negative subtype of breast cancer. In addition, it was found that HER2 overexpression in MDA-MB-231 cell increased GPER1, which may help explain protumor effect of GPER1 in HER2-overexpressed patients. The overall results suggested that the expression of GPER1 has distinct prognostic values in HER2-positive and HER2-negative breast cancer patients.

Keywords: GPER1, breast cancer, HER2, CREB, cAMP response element-binding protein

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