Cytoplasmic G Protein-Coupled Estrogen Receptor 1 as a Prognostic Indicator of Breast Cancer: A Meta-Analysis

Purpose: To determine whether G protein-coupled estrogen receptor 1 (GPER1) is a suitable biomarker to predict the treatment outcome of breast cancer (BC). Methods: A meta-analysis of the literature was performed to clarify the correlation between GPER1 protein expression and BC outcome. The relationship between GPER1 mRNA expression and survival was analyzed using Breast Cancer Gene-Expression Miner (bc-GenExMiner) v4.6 software. Results: Six studies involving 2697 patients were included in the meta-analysis. Four studies reported the correlation between GPER1 protein expression and relapse-free survival (RFS) and 4 others reported the impact of GPER1 protein expression on overall survival (OS). The results showed that high GPER1 protein expression was not associated with RFS (hazard ratio [HR] = 1.58; 95% confidence interval [CI] = 0.71-3.48; P = .26) or OS (HR = 1.18; 95% CI = 0.64-2.18; P = .60). Subgroup analysis suggested that nuclear expression of GPER1 was not associated with OS (HR = 0.91; 95% CI = 0.77-1.08; P = .30), but high expression of cytoplasmic GPER1 was significantly associated with longer OS (HR = 0.69; 95% CI = 0.55-0.86; P = .001). Furthermore, the association of GPER1 mRNA and OS of BC patients was analyzed using bc-GenExMiner v4.6. Two data sets involving 4016 patients were included in the analysis. The targeted prognostic analysis results showed that high mRNA expression of GPER1 was predictive of better OS in BC patients (HR = 0.71; 95% CI = 0.59-0.86; P = .0005), which was remarkably similar to the result of cytoplasmic GPER1. Further subgroup analysis demonstrated that high mRNA expression of GPER1 was predictive of better OS in estrogen receptor (ER)-positive, but not ER-negative or triple-negative BC patients. Conclusions: High mRNA and cytoplasmic protein expression of GPER1 were predictive of better OS of BC patients.