Clinical Relevance Of GPER/GPR30in Ovarian Cancer

Objectives:Ovarian cancer with high mortality is one common subset of gynecological cancers. Further, G protein-coupled estrogen receptor (GPER/GPR30) is a novel estrogen receptor that mediates signaling pathway of estrogen. Current studies suggest that GPER/GPR30expression predicts poor outcome in breast cancer. Nevertheless, the impact of GPER/GPR30expression in ovarian cancer is unclear. The purpose of this study was to demonstrate the correlation of GPER/GPR30expression (protein/mRNA) and clinicopathological features, especially its impact of prognosis, and elucidate the distribution of GPER/GPR30in ovarian cancer cell.Methods:The expression level of GPER/GPR30protein was determined by using immunohistochemistry in104epithelial ovarian cancers, while analysis of GPER/GPR30mRNA was performed via RT-PCR in22benign tissues and44epithelial ovarian cancers. Thus we correlated GPER/GPR30expression with clinicopathological characteristics and outcome of ovarian cancer patients. Further, localization of GPER/GPR30was described by using immunofluorescence.Results:GPER/GPR30mRNA expression was significantly higher in ovarian cancer than that in benign tissue (p=0.044). Furthermore, there was significant difference of GPER/GPR30expression in variant subtype of ovarian cancer (p=0.013). The expression of GPER/GPR30in advanced ovarian cancer was significantly higher than that in early stage (FIGO stage, p=0.001; histological grading, p=0.018), but was not associated with the age. GPER/GPR30expression at protein level was an independent poorly prognostic factor in regard to overall survival (p=0.005) and5-year disease-free survival (p=0.007). In addition, GPER/GPR30expression-positive predicted higher risk of death in advanced ovarian cancer patients (HR,3.037; p=0.019), while GPER/GPR30was not independently correlated with recurrence in patients diagnosed at advanced stage. Intracellular GPER/GPR30was determined in SKOV-3cells. Conclusion:The expression of GPER/GPR30was significantly related with lower OS and poorer5-year DFS of ovarian cancer patients. Furthermore, GPER/GPR30was an independent poor prognosis in regard to OS, whereas GPER/GPR30expression was not significantly associated with5-year DFS in advanced ovarian cancer. In addition, intracellular GPER/GPR30aggregating toward nucleus suggested a potential regulation for the progression of ovarian cancer.