The prognostic values of estrogen receptor alpha and beta in patients with gastroesophageal cancer: A meta-analysis.

Background: Published studies have investigated the prognostic roles of estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) in gastroesophageal cancer patients with the controversial results. The aim of the study was to systematically evaluate the impacts of ER alpha and ER beta on the overall survival (OS) in patients. Method: Relevant eligible studies were extracted from PubMed, Embase, Web of Science, CNKI and Wanfang databases (from the start date to November 2018) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. HR (hazard ratio) with 95% confidence intervals (CIs) were used to assess the prognostic values of ER alpha and ER beta for OS in patients. Results: High ER alpha expression was associated with poor OS (HR=1.58, 95% CI=1.29-1.94, P<.001) and ER beta with better OS (HR=0.56, 95% CI=0.37-0.83, P=.004) in gastroesophageal cancer. Furthermore, unfavorable OS was found in Chinese gastroesophageal patients with higher ER alpha expression (HR=1.57, 95% CI=1.25-1.96, P<.001) and better OS with higher ER beta expression (HR=0.51, 95% CI=0.31-0.83, P<.01) in our subgroup analysis. Meanwhile, worse OS was found in esophageal squamous cell carcinoma (ESCC) patients with high ER alpha expression (HR=1.74, 95% CI=1.33-2.26, P<.001), and favorable OS in ESCC with ER beta overexpression (HR=0.40, 95% CI=0.31-0.52, P<.001). Besides, high ER alpha expression was associated with lower tumor differentiation in ESCC (OR=1.64; 95% CI=1.02-2.64, P=.04) and ER beta was linked with better tumor differentiation in gastric adenocarcinoma (GCA) (OR=0.49; 95% CI=0.26-0.94, P=.03). Conclusions: ER alpha and ER beta might serve as potential prognostic biomarkers for gastroesophageal cancer patients. ER alpha overexpression predicted poor OS and lower tumor differentiation, and ER beta suggested favorable OS and better tumor differentiation. Further related studies should be performed to test these results.