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pmid:31028714

Downregulation of G Protein-Coupled Estrogen Receptor (GPER) is Associated with Reduced Prognosis in Patients with Gastric Cancer.

Shan Tian · Na Zhan · Ruixue Li · Weiguo Dong

Medical science monitor : international medical journal of experimental and clinical research · 2019 doi:10.12659/MSM.913634

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Experiment

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Data

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title
Downregulation of G Protein-Coupled Estrogen Receptor (GPER) is Associated with Reduced Prognosis in Patients with Gastric Cancer.
doi
10.12659/MSM.913634
pmid
31028714
authors array · 4 items
[0]
Shan Tian
[1]
Na Zhan
[2]
Ruixue Li
[3]
Weiguo Dong
journal
Medical science monitor : international medical journal of experimental and clinical research
year
2019
abstract
BACKGROUND This study is aimed to investigate the prognostic significance of the expression of G protein-coupled estrogen receptor (GPER) in gastric cancer tissue using bioinformatics data and immunohistochemistry. MATERIAL AND METHODS Expression of GPER mRNA in gastric cancer tissues and normal adjacent tissues was investigated using data from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and Oncomine database. Kaplan-Meier Plotter identified the association between GPER mRNA and prognosis. Correlation between GPER mRNA and DNA methylation used the cBioPortal for Cancer Genomics and the MethHC website. Genes co-expressed with GPER were identified from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) underwent FunRich analysis. Immunohistochemistry and Western blot evaluated GPER protein expression in tissue microarrays (TMAs) and gastric cancer cell lines. RESULTS GPER mRNA and protein levels were significantly lower in gastric cancer tissue and cells lined when compared with normal tissues and cells. The results from GSE15459 showed that patients with low levels of GPER mRNA had a reduced overall survival (OS) (P=0.013) and disease-free survival (DFS) (P=0.019). A negative correlation (r=-0.611) between GPER mRNA and DNA methylation was found using the cBioPortal and MethHC. Co-expressed epithelial-mesenchymal transformation (EMT) genes were enriched with GPER (P<0.0001). Cox regression analysis showed that GPER protein expression was an independent prognostic factor (P=0.035) CONCLUSIONS Downregulation of GPER predicts poor prognosis in gastric cancer. GPER may act as a tumor suppressor through the regulation of EMT in gastric cancer.
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The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3).
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sections[12] "The prognostic value of GPER mRNA expression in gastric cancer" paragraph 2
quote
The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3).
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GPER mRNA expression data were downloaded from the public database of RNA sequencing data in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).
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sections[7] "Bioinformatics analysis" paragraph 2
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GPER mRNA expression data were downloaded from the public database of RNA sequencing data in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).
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Affymetrix gene expression array data for cardia and non-cardia gastric cancer samples
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The diagnostic value of G protein-coupled estrogen receptor (GPER) for gastric cancer from six datasets.
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The diagnostic value of GPER mRNA expression in gastric cancer
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The diagnostic value of G protein-coupled estrogen receptor (GPER) for gastric cancer from six datasets.
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70.97%
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70.09%
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GSE29272
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92.54%
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85.07%
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Correlation between the expression of G protein-coupled estrogen receptor (GPER) protein and clinicopathological factors.
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Correlations between GPER protein expression in gastric cancer tissue and clinicopathological features in patients with gastric cancer
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Correlation between the expression of G protein-coupled estrogen receptor (GPER) protein and clinicopathological factors.
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Cox regression of G protein-coupled estrogen receptor (GPER) protein expression and overall survival of patients with gastric cancer.
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Prognostic significance of GPER protein expression in gastric cancer
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Cox regression of G protein-coupled estrogen receptor (GPER) protein expression and overall survival of patients with gastric cancer.
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The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3).
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GPER mRNA expression data were downloaded from the public database of RNA sequencing data in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).
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cancer tissue using bioinformatics data and immunohistochemistry. MATERIAL AND METHODS Expression of GPER mRN
[1]
noma (TCGA-STAD) underwent FunRich analysis. Immunohistochemistry and Western blot evaluated GPER protein expr
[2]
cal features in patients with gastric cancer Immunohistochemistry showed that GPER protein expression differed
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%) showed low expression levels of GPER. The immunohistochemistry results showed that GPER was expressed at lo
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t FunRich analysis. Immunohistochemistry and Western blot evaluated GPER protein expression in tissue
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The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31028714", "kind": "science-record", "revision": 7, "content_hash": "sha256:ecdbc8477c745283ddd8856076c5028380fb33b4ef123f91579966787af85109", "created_at": "2026-11-01T15:40:44Z", "updated_at": "2026-11-01T21:22:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Downregulation of G Protein-Coupled Estrogen Receptor (GPER) is Associated with Reduced Prognosis in Patients with Gastric Cancer.", "doi": "10.12659/MSM.913634", "pmid": "31028714", "authors": ["Shan Tian", "Na Zhan", "Ruixue Li", "Weiguo Dong"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2019, "abstract": "BACKGROUND This study is aimed to investigate the prognostic significance of the expression of G protein-coupled estrogen receptor (GPER) in gastric cancer tissue using bioinformatics data and immunohistochemistry. MATERIAL AND METHODS Expression of GPER mRNA in gastric cancer tissues and normal adjacent tissues was investigated using data from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and Oncomine database. Kaplan-Meier Plotter identified the association between GPER mRNA and prognosis. Correlation between GPER mRNA and DNA methylation used the cBioPortal for Cancer Genomics and the MethHC website. Genes co-expressed with GPER were identified from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) underwent FunRich analysis. Immunohistochemistry and Western blot evaluated GPER protein expression in tissue microarrays (TMAs) and gastric cancer cell lines. RESULTS GPER mRNA and protein levels were significantly lower in gastric cancer tissue and cells lined when compared with normal tissues and cells. The results from GSE15459 showed that patients with low levels of GPER mRNA had a reduced overall survival (OS) (P=0.013) and disease-free survival (DFS) (P=0.019). A negative correlation (r=-0.611) between GPER mRNA and DNA methylation was found using the cBioPortal and MethHC. Co-expressed epithelial-mesenchymal transformation (EMT) genes were enriched with GPER (P<0.0001). Cox regression analysis showed that GPER protein expression was an independent prognostic factor (P=0.035) CONCLUSIONS Downregulation of GPER predicts poor prognosis in gastric cancer. GPER may act as a tumor suppressor through the regulation of EMT in gastric cancer.", "claims": [{"id": "claim-method", "statement": "The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31028714", "locator": "sections[12] \"The prognostic value of GPER mRNA expression in gastric cancer\" paragraph 2", "quote": "The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GPER mRNA expression data were downloaded from the public database of RNA sequencing data in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31028714", "locator": "sections[7] \"Bioinformatics analysis\" paragraph 2", "quote": "GPER mRNA expression data were downloaded from the public database of RNA sequencing data in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31028714"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE15459"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE15459"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31028714", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/MSM.913634", "sha256": 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"identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:31028714:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8aa3295c70342f632c9244749a5fbd3123cddafbeb979ac8c93ee1321b2ba672", "bytes": 831, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t1-medscimonit-25-3115", "version": null, "note": "The diagnostic value of G protein-coupled estrogen receptor (GPER) for gastric cancer from six datasets.", "structure": {"pmcid": "PMC6503750", "section_index": 11, "section_title": "The diagnostic value of GPER mRNA expression in gastric cancer", "row_count": 7, "column_count": 7}, "table": {"label": "Table 1", "caption": "The diagnostic value of G protein-coupled estrogen receptor (GPER) for gastric cancer from six datasets.", "rows": [["Study", "Cut-off value", 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"read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#t2-medscimonit-25-3115", "version": null, "note": "Correlation between the expression of G protein-coupled estrogen receptor (GPER) protein and clinicopathological factors.", "structure": {"pmcid": "PMC6503750", "section_index": 15, "section_title": "Correlations between GPER protein expression in gastric cancer tissue and clinicopathological features in patients with gastric cancer", "row_count": 18, "column_count": 6}, "table": {"label": "Table 2", "caption": "Correlation between the expression of G protein-coupled estrogen receptor (GPER) protein and clinicopathological factors.", "rows": [["Parameter", "GPER expression", "χ2-value", "P-value"], ["Low (n=58)", "High (n=26)"], ["Gender", "Male", "46", "9", "15.865", "<0.0001*"], ["Female", "12", "17"], ["Age (years)", "≤60", "35", "17", "1.93", "0.666"], [">60", "23", "9"], ["Tumor diameter", "<5 cm", "40", "18", "0.001", "0.981"], ["≥5 cm", "18", "8"], ["T stage", "T1–T2", "18", "9", "0.106", "0.745"], ["T3–T4", "40", "17"], ["Grade (G)", "G1", "25", "22", "12.525", "<0.0001*"], ["G2–G3", "33", "4"], ["N stage", "N0", "19", "11", "0.713", "0.398"], ["N1–N3", "39", "15"], ["M stage", "M0", "39", "22", "2.725", "0.099"], ["M1", "19", "4"], ["TNM stage", "I–II", "27", "15", "0.891", "0.345"], ["II–IV", "31", "11"]], "row_count": 18, "column_count": 6, "numeric_cells": 55, "header_rows": 2, "locator": "section[15]/table-wrap[1]#t2-medscimonit-25-3115"}}, {"id": "asset:table:pmid:31028714:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:78db09d907d67c1bc384b2497f9c98f1a7e50d1423dc146fb197989225205bdb", "bytes": 1178, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#t3-medscimonit-25-3115", "version": null, "note": "Cox regression of G protein-coupled estrogen receptor (GPER) protein expression and overall survival of patients with gastric cancer.", "structure": {"pmcid": "PMC6503750", "section_index": 16, "section_title": "Prognostic significance of GPER protein expression in gastric cancer", "row_count": 11, "column_count": 5}, "table": {"label": "Table 3", "caption": "Cox regression of G protein-coupled estrogen receptor (GPER) protein expression and overall survival of patients with gastric cancer.", "rows": [["Clinical factor", "Univariate analysis", "Multivariate analysis"], ["P-value", "HR (95% CI)", "P-value", "HR (95% CI)"], ["Gender (Male vs. Female)", "0.736", "0.859 (0.349–2.103)", "–", "–"], ["Age (≤60 vs. >60)", "0.349", "1.538 (0.572–4,138)", "–", "–"], ["T stage (T1–T2 vs. T3–T4)", "0.045*", "7.785 (1.042–58.08)", "0.24", "3.981 (0.398–39.801)"], ["N stage (N0 vs. N1–N3)", "0.05", "2.973 (1.001–8.832)", "–", "–"], ["M stage (M0 vs. M1)", "0.024*", "2.669 (1.135–6.278)", "0.77", "0.854 (0.296–2.463)"], ["Grade (G) (G1 vs. G2–G3)", "0.172", 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"The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3)."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-4", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "χ2"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE29272", "GSE15459"], "resolved_accessions": ["GSE29272", "GSE15459"], "statements": ["GPER mRNA expression data were downloaded from the public database of RNA sequencing data in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)."], "basis": "The paper names GSE29272, GSE15459 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:31028714", "data:geo:GSE15459", "asset:table:pmid:31028714:1", "asset:table:pmid:31028714:2", "asset:table:pmid:31028714:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE15459"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:14:30Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 31248, "completion_tokens": 1490, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:31028714", "type": "paper", "label": "pmid:31028714"}, {"id": "source:pmid:31028714", "type": "manuscript", "label": "PMID 31028714 full text"}, {"id": "data:geo:GSE15459", "type": "dataset", "label": "GEO GSE15459"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31028714", "type": "paper", "label": "pmid:31028714"}, {"id": "source:pmid:31028714", "type": "manuscript", "label": "PMID 31028714 full text"}, {"id": "data:geo:GSE15459", "type": "dataset", "label": "GEO GSE15459"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31028714", "type": "extraction", "used": ["source:pmid:31028714"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE15459", "type": "accession_resolution", "used": ["data:geo:GSE15459"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:31028714", "parent_hash": "sha256:aba34bf4358f7f2ddd9607d7ad4398c016f00dd4841cecb6e2573811cbf78c70", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE15459 not downloaded", "asset:data:geo:GSE29272 licence not read", "asset:data:geo:GSE29272 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["cancer tissue using bioinformatics data and immunohistochemistry. MATERIAL AND METHODS Expression of GPER mRN", "noma (TCGA-STAD) underwent FunRich analysis. Immunohistochemistry and Western blot evaluated GPER protein expr", "cal features in patients with gastric cancer Immunohistochemistry showed that GPER protein expression differed", "%) showed low expression levels of GPER. The immunohistochemistry results showed that GPER was expressed at lo"], "order_basis": "paper_text_order:280", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["t FunRich analysis. Immunohistochemistry and Western blot evaluated GPER protein expression in tissue"], "order_basis": "paper_text_order:880", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The website of the Kaplan-Meier Plotter was used to evaluate the prognostic value of GPER mRNA in gastric cancer. Kaplan-Meier survival analysis based on GSE15459 (n=200) showed that higher expression levels of GPER mRNA were significantly associated with improved overall survival (OS) (P=0.013, HR=0.58) when compared with patients with gastric cancer and low levels of expression of GPER mRNA (Figure 3)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}