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pmid:39717045

Exploring the potential role of ENPP2 in polycystic ovary syndrome and endometrial cancer through bioinformatic analysis.

Xumin Zhang · Jianrong Liu · Chunmei Bai · Yang Li · Yanxin Fan

PeerJ · 2024 doi:10.7717/peerj.18666

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Experiment

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Data

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Analysis

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Exploring the potential role of ENPP2 in polycystic ovary syndrome and endometrial cancer through bioinformatic analysis.
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10.7717/peerj.18666
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39717045
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Xumin Zhang
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Jianrong Liu
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Chunmei Bai
[3]
Yang Li
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Yanxin Fan
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PeerJ
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2024
abstract
Background: Growing evidence indicates a significant correlation between polycystic ovary syndrome (PCOS) and endometrial carcinoma (EC); nevertheless, the fundamental molecular mechanisms involved continue to be unclear. Methods: Initially, differential analysis, the least absolute shrinkage and selection operator (LASSO) regression, and support vector machine-recursive feature elimination (SVM-RFE) algorithms were employed to identify candidate genes associated with ferroptosis in PCOS. Subsequently, the TCGA-UCEC data were utilized to pinpoint the core gene. Then, the expression of ENPP2 in granulosa cells and endometrium of PCOS was validated using real-time PCR (RT-qPCR). Additionally, we investigated the role of ENPP2 in the progression from PCOS to EC through western blotting (WB), colony formation assay, cell scratch assay, transwell assay, and immunofluorescence (IF). Subsequently, ENPP2 gene set enrichment analysis (GSEA) analyses were conducted to identify common pathways involved in PCOS and EC, which were then verified by RT-qPCR. Finally, immune infiltration and the tumor microenvironment (TME) were explored to examine the involvement of ENPP2 in EC progression. Results: The datasets TCGA-UCEC (pertaining to EC), GSE34526, GSE137684, and GSE6798 (related to PCOS) were procured and subjected to analysis. The gene ENPP2 has been recognized as the shared element connecting PCOS and EC. Next, we observed a significant downregulation of ENPP2 expression in the granulosa cells in PCOS compared to the normal patients, while an upregulation of ENPP2 expression was observed in the endometrium of hyperandrogenic PCOS patients relative to the normal. In vitro, the WB revealed that 5-dihydrotestosterone (DHT) upregulated ENPP2 expression in Ishikawa and HEC-1-A cells. Additionally, we found that ENPP2 promoted the proliferation, migration, and invasion of Ishikawa and HEC-1-A cells. Subsequently, we discovered that overexpressed ENPP2 may lead to an increase in CYP19A1 (aromatase) and AR mRNA level. IF demonstrated that ENPP2 increased the expression of AR, suggesting a regulatory role for ENPP2 in hormonal response within PCOS and EC. Our findings indicated a significant correlation between ENPP2 expression and the modulation of immune responses.
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Two distinct algorithms, LASSO logistic regression and SVM-RFE, were utilized to assess nine candidate genes linked to PCOS.
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m of PCOS was validated using real-time PCR (RT-qPCR). Additionally, we investigated the role of
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39717045", "kind": "science-record", "revision": 4, "content_hash": "sha256:b04796d1050299276cedb8ab8f72b8cccf66af544aa6cfa6b18623ed0934497f", "created_at": "2026-11-01T20:30:02Z", "updated_at": "2026-11-01T22:55:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring the potential role of ENPP2 in polycystic ovary syndrome and endometrial cancer through bioinformatic analysis.", "doi": "10.7717/peerj.18666", "pmid": "39717045", "authors": ["Xumin Zhang", "Jianrong Liu", "Chunmei Bai", "Yang Li", "Yanxin Fan"], "journal": "PeerJ", "year": 2024, "abstract": "Background: Growing evidence indicates a significant correlation between polycystic ovary syndrome (PCOS) and endometrial carcinoma (EC); nevertheless, the fundamental molecular mechanisms involved continue to be unclear.\nMethods: Initially, differential analysis, the least absolute shrinkage and selection operator (LASSO) regression, and support vector machine-recursive feature elimination (SVM-RFE) algorithms were employed to identify candidate genes associated with ferroptosis in PCOS. Subsequently, the TCGA-UCEC data were utilized to pinpoint the core gene. Then, the expression of ENPP2 in granulosa cells and endometrium of PCOS was validated using real-time PCR (RT-qPCR). Additionally, we investigated the role of ENPP2 in the progression from PCOS to EC through western blotting (WB), colony formation assay, cell scratch assay, transwell assay, and immunofluorescence (IF). Subsequently, ENPP2 gene set enrichment analysis (GSEA) analyses were conducted to identify common pathways involved in PCOS and EC, which were then verified by RT-qPCR. Finally, immune infiltration and the tumor microenvironment (TME) were explored to examine the involvement of ENPP2 in EC progression.\nResults: The datasets TCGA-UCEC (pertaining to EC), GSE34526, GSE137684, and GSE6798 (related to PCOS) were procured and subjected to analysis. The gene ENPP2 has been recognized as the shared element connecting PCOS and EC. Next, we observed a significant downregulation of ENPP2 expression in the granulosa cells in PCOS compared to the normal patients, while an upregulation of ENPP2 expression was observed in the endometrium of hyperandrogenic PCOS patients relative to the normal. In vitro, the WB revealed that 5-dihydrotestosterone (DHT) upregulated ENPP2 expression in Ishikawa and HEC-1-A cells. Additionally, we found that ENPP2 promoted the proliferation, migration, and invasion of Ishikawa and HEC-1-A cells. Subsequently, we discovered that overexpressed ENPP2 may lead to an increase in CYP19A1 (aromatase) and AR mRNA level. IF demonstrated that ENPP2 increased the expression of AR, suggesting a regulatory role for ENPP2 in hormonal response within PCOS and EC. Our findings indicated a significant correlation between ENPP2 expression and the modulation of immune responses.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were identified using the R package “limma”. Two distinct algorithms, LASSO logistic regression and SVM-RFE, were utilized to assess nine candidate genes linked to PCOS.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39717045", "locator": "sections[3] \"Data collection\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were identified using the R package “limma”."}, {"asset": "source:pmid:39717045", "locator": "sections[19] \"Diagnostic biomarkers of PCOS\" paragraph 2", "quote": "Two distinct algorithms, LASSO logistic regression and SVM-RFE, were utilized to assess nine candidate genes linked to PCOS."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data are available in the Supplemental Files and at NCBI GEO: GSE6798, GSE34526 and GSE137684", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39717045", "locator": "sections[27] \"Additional Information and Declarations\" paragraph 5", "quote": "The raw data are available in the Supplemental Files and at NCBI GEO: GSE6798, GSE34526 and GSE137684"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:39717045"], "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:GSE137684"], "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:GSE137684"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39717045", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.18666", "sha256": 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Polycystic Ovary Syndrome Patients with and without Insulin Resistance:  Identification of Susceptibility Gene Sets through Network Analysis", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE6798", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6798", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE6798", "version": null, "note": "The raw data are available in the Supplemental Files and at NCBI GEO: GSE6798, GSE34526 and GSE137684", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data are available in the Supplemental Files and at NCBI GEO: GSE6798, GSE34526 and GSE137684", 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Additionally, we investigated the role of", "in PCOS and EC, which were then verified by RT-qPCR. Finally, immune infiltration and the tumor", "f PCOS was validated using real-time PCR (RT-qPCR). Additionally, we investigated the role of", "PCOS and EC, which were then verified by RT-qPCR. 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