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pmid:30813939

Comprehensive bioinformatics analysis of acquired progesterone resistance in endometrial cancer cell line.

Wenzhi Li · Shufen Wang · Chunping Qiu · Zhiming Liu · Qing Zhou · Deshui Kong · Xiaohong Ma · Jie Jiang

Journal of translational medicine · 2019 doi:10.1186/s12967-019-1814-6

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Experiment

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Data

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:30813939
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title
Comprehensive bioinformatics analysis of acquired progesterone resistance in endometrial cancer cell line.
doi
10.1186/s12967-019-1814-6
pmid
30813939
authors array · 8 items
[0]
Wenzhi Li
[1]
Shufen Wang
[2]
Chunping Qiu
[3]
Zhiming Liu
[4]
Qing Zhou
[5]
Deshui Kong
[6]
Xiaohong Ma
[7]
Jie Jiang
journal
Journal of translational medicine
year
2019
abstract
BACKGROUND: Progesterone resistance is a problem in endometrial carcinoma, and its underlying molecular mechanisms remain poorly understood. The aim of this study was to elucidate the molecular mechanisms of progesterone resistance and to identify the key genes and pathways mediating progesterone resistance in endometrial cancer using bioinformatics analysis. METHODS: We developed a stable MPA (medroxyprogesterone acetate)-resistant endometrial cancer cell subline named IshikawaPR. Microarray analysis was used to identify differentially expressed genes (DEGs) from triplicate samples of Ishikawa and IshikawaPR cells. PANTHER, DAVID and Metascape were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and cBioPortal for progesterone receptor (PGR) coexpression analysis. GEO microarray (GSE17025) was utilized for validation. The protein-protein interaction network (PPI) and modular analyses were performed using Metascape and Cytoscape. Further validation were performed by real-time polymerase chain reaction (RT-PCR). RESULTS: In total, 821 DEGs were found and further analyzed by GO, KEGG pathway enrichment and PPI analyses. We found that lipid metabolism, immune system and inflammation, extracellular environment-related processes and pathways accounted for a significant portion of the enriched terms. PGR coexpression analysis revealed 7 PGR coexpressed genes (ANO1, SOX17, CGNL1, DACH1, RUNDC3B, SH3YL1 and CRISPLD1) that were also dramatically changed in IshikawaPR cells. Kaplan-Meier survival statistics revealed clinical significance for 4 out of 7 target genes. Furthermore, 8 hub genes and 4 molecular complex detections (MCODEs) were identified. CONCLUSIONS: Using microarray and bioinformatics analyses, we identified DEGs and determined a comprehensive gene network of progesterone resistance. We offered several possible mechanisms of progesterone resistance and identified therapeutic and prognostic targets of progesterone resistance in endometrial cancer.
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Kaplan–Meier curves for target genes were generated with the online tool Kaplan–Meier Plotter (http://www.kmplot.com/). A total of 542 RNA-seq data samples of uterine corpus endometrial carcinoma were interrogated. The patients were split into 2 groups (high vs. low) based on the expression level.
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sections[5] "PGR coexpression analysis and validation by bioinformatics" paragraph 3
quote
Kaplan–Meier curves for target genes were generated with the online tool Kaplan–Meier Plotter (http://www.kmplot.com/). A total of 542 RNA-seq data samples of uterine corpus endometrial carcinoma were interrogated. The patients were split into 2 groups (high vs. low) based on the expression level.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Endometrial cancer cell line with acquired resistance to medroxyprogesterone acetate
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Gene Expression Analysis of Stage I Endometrial Cancers
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Top 10 GO enrichment analyses of up-regulated and down-regulated DEGs
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Top 5 KEGG pathway enrichment of up-regulated and down-regulated DEGs sorted by p-value and count of hit-genes
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PGR coexpression analysis and validation
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Distinguishing and validation of 7 PGR co-expressed genes among DEGs
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3.00E−06
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0.00046
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0.39
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0.285
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0.79
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0.27
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0.58
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0.54
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0.416
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< 0.01
[7]
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0.235
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0.73
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0.21
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8 hub genes (degree ≥ 15) selected from PPI network according to degree
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8 hub genes (degree ≥ 15) selected from PPI network according to degree
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Top 15 GO enrichments of the 4 MCODEs related genes
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Protein-protein interaction network (PPI) and modular analysis
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Top 15 GO enrichments of the 4 MCODEs related genes
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[1]
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Positive regulation of neutrophil chemotaxis
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3.13
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Neuropeptide signaling pathway
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G-protein coupled receptor signaling pathway
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GO:0005887
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GO:0071556
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Integral component of lumenal side of endoplasmic reticulum membrane
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2.96
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GO:0008395
[1]
Steroid hydroxylase activity
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GO:0020037
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3.96
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Top 10 KEGG pathway enrichment of the 4 MCODEs related genes
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Protein-protein interaction network (PPI) and modular analysis
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Table 6
caption
Top 10 KEGG pathway enrichment of the 4 MCODEs related genes
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section[13]/table-wrap[3]#Tab6
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Kaplan–Meier curves for target genes were generated with the online tool Kaplan–Meier Plotter (http://www.kmplot.com/). A total of 542 RNA-seq data samples of uterine corpus endometrial carcinoma were interrogated. The patients were split into 2 groups (high vs. low) based on the expression level.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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etrial cancer cell subline named IshikawaPR. Microarray analysis was used to identify differentially
[1]
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30813939", "kind": "science-record", "revision": 7, "content_hash": "sha256:3c8ae4b6c0bc85bee2e31138976d42d346e899b8035fbc15e58177bfcadcb72d", "created_at": "2026-11-01T15:40:42Z", "updated_at": "2026-11-01T22:00:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive bioinformatics analysis of acquired progesterone resistance in endometrial cancer cell line.", "doi": "10.1186/s12967-019-1814-6", "pmid": "30813939", "authors": ["Wenzhi Li", "Shufen Wang", "Chunping Qiu", "Zhiming Liu", "Qing Zhou", "Deshui Kong", "Xiaohong Ma", "Jie Jiang"], "journal": "Journal of translational medicine", "year": 2019, "abstract": "BACKGROUND: Progesterone resistance is a problem in endometrial carcinoma, and its underlying molecular mechanisms remain poorly understood. The aim of this study was to elucidate the molecular mechanisms of progesterone resistance and to identify the key genes and pathways mediating progesterone resistance in endometrial cancer using bioinformatics analysis.\nMETHODS: We developed a stable MPA (medroxyprogesterone acetate)-resistant endometrial cancer cell subline named IshikawaPR. Microarray analysis was used to identify differentially expressed genes (DEGs) from triplicate samples of Ishikawa and IshikawaPR cells. PANTHER, DAVID and Metascape were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and cBioPortal for progesterone receptor (PGR) coexpression analysis. GEO microarray (GSE17025) was utilized for validation. The protein-protein interaction network (PPI) and modular analyses were performed using Metascape and Cytoscape. Further validation were performed by real-time polymerase chain reaction (RT-PCR).\nRESULTS: In total, 821 DEGs were found and further analyzed by GO, KEGG pathway enrichment and PPI analyses. We found that lipid metabolism, immune system and inflammation, extracellular environment-related processes and pathways accounted for a significant portion of the enriched terms. PGR coexpression analysis revealed 7 PGR coexpressed genes (ANO1, SOX17, CGNL1, DACH1, RUNDC3B, SH3YL1 and CRISPLD1) that were also dramatically changed in IshikawaPR cells. Kaplan-Meier survival statistics revealed clinical significance for 4 out of 7 target genes. Furthermore, 8 hub genes and 4 molecular complex detections (MCODEs) were identified.\nCONCLUSIONS: Using microarray and bioinformatics analyses, we identified DEGs and determined a comprehensive gene network of progesterone resistance. We offered several possible mechanisms of progesterone resistance and identified therapeutic and prognostic targets of progesterone resistance in endometrial cancer.", "claims": [{"id": "claim-method", "statement": "Kaplan–Meier curves for target genes were generated with the online tool Kaplan–Meier Plotter (http://www.kmplot.com/). A total of 542 RNA-seq data samples of uterine corpus endometrial carcinoma were interrogated. The patients were split into 2 groups (high vs. low) based on the expression level.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30813939", "locator": "sections[5] \"PGR coexpression analysis and validation by bioinformatics\" paragraph 3", "quote": "Kaplan–Meier curves for target genes were generated with the online tool Kaplan–Meier Plotter (http://www.kmplot.com/). A total of 542 RNA-seq data samples of uterine corpus endometrial carcinoma were interrogated. The patients were split into 2 groups (high vs. low) based on the expression level."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30813939", "locator": "sections[23] \"ack\" paragraph 1", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "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:30813939"], "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:GSE121367"], "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:GSE121367"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30813939", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-019-1814-6", "sha256": 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