Dataset Information

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

ABSTRACT:

Background

Published studies have investigated the prognostic roles of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in gastroesophageal cancer patients with the controversial results. The aim of the study was to systematically evaluate the impacts of ERα and ERβ 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 ERα and ERβ for OS in patients.

Results

High ERα expression was associated with poor OS (HR = 1.58, 95% CI = 1.29-1.94, P < .001) and ERβ 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 ERα expression (HR = 1.57, 95% CI = 1.25-1.96, P < .001) and better OS with higher ERβ 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 ERα expression (HR = 1.74, 95% CI = 1.33-2.26, P < .001), and favorable OS in ESCC with ERβ overexpression (HR = 0.40, 95% CI = 0.31-0.52, P < .001). Besides, high ERα expression was associated with lower tumor differentiation in ESCC (OR = 1.64; 95% CI = 1.02-2.64, P = .04) and ERβ was linked with better tumor differentiation in gastric adenocarcinoma (GCA) (OR = 0.49; 95% CI = 0.26-0.94, P = .03).

Conclusions

ERα and ERβ might serve as potential prognostic biomarkers for gastroesophageal cancer patients. ERα overexpression predicted poor OS and lower tumor differentiation, and ERβ suggested favorable OS and better tumor differentiation. Further related studies should be performed to test these results.

SUBMITTER: Zhang D

PROVIDER: S-EPMC6867741 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Dongyun D Ku Jianwei J Yi Yingjie Y Zhang Junhui J Liu Rongzhi R Tang Nianya N

Medicine 20191101 46

<h4>Background</h4>Published studies have investigated the prognostic roles of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in gastroesophageal cancer patients with the controversial results. The aim of the study was to systematically evaluate the impacts of ERα and ERβ on the overall survival (OS) in patients.<h4>Method</h4>Relevant eligible studies were extracted from PubMed, Embase, Web of Science, CNKI and Wanfang databases (from the start date to November 2018) following t ...[more]

PMID: 31725654

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Project description:BackgroundBreast cancer (BC) is highly heterogeneous with ~ 60-70% of estrogen receptor positive BC patient's response to anti-hormone therapy. Estrogen receptors (ERs) play an important role in breast cancer progression and treatment. Estrogen related receptors (ERRs) are a group of nuclear receptors which belong to orphan nuclear receptors, which have sequence homology with ERs and share target genes. Here, we investigated the possible role and clinicopathological importance of ERRβ in breast cancer.MethodsEstrogen related receptor β (ERRβ) expression was examined using tissue microarray slides (TMA) of Breast Carcinoma patients with adjacent normal by immunohistochemistry and in breast cancer cell lines. In order to investigate whether ERRβ is a direct target of ERα, we investigated the expression of ERRβ in short hairpin ribonucleic acid knockdown of ERα breast cancer cells by western blot, qRT-PCR and RT-PCR. We further confirmed the binding of ERα by electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), Re-ChIP and luciferase assays. Fluorescence-activated cell sorting analysis (FACS) was performed to elucidate the role of ERRβ in cell cycle regulation. A Kaplan-Meier Survival analysis of GEO dataset was performed to correlate the expression of ERRβ with survival in breast cancer patients.ResultsTissue microarray (TMA) analysis showed that ERRβ is significantly down-regulated in breast carcinoma tissue samples compared to adjacent normal. ER + ve breast tumors and cell lines showed a significant expression of ERRβ compared to ER-ve tumors and cell lines. Estrogen treatment significantly induced the expression of ERRβ and it was ERα dependent. Mechanistic analyses indicate that ERα directly targets ERRβ through estrogen response element and ERRβ also mediates cell cycle regulation through p18, p21cip and cyclin D1 in breast cancer cells. Our results also showed the up-regulation of ERRβ promoter activity in ectopically co-expressed ERα and ERRβ breast cancer cell lines. Fluorescence-activated cell sorting analysis (FACS) showed increased G0/G1 phase cell population in ERRβ overexpressed MCF7 cells. Furthermore, ERRβ expression was inversely correlated with overall survival in breast cancer. Collectively our results suggest cell cycle and tumor suppressor role of ERRβ in breast cancer cells which provide a potential avenue to target ERRβ signaling pathway in breast cancer.ConclusionOur results indicate that ERRβ is a negative regulator of cell cycle and a possible tumor suppressor in breast cancer. ERRβ could be therapeutic target for the treatment of breast cancer.

Dataset Information

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

Background

Method

Results

Conclusions

Publications

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

Similar Datasets

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