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pmid:39934690

Identification of critical biomarkers and immune infiltration in preeclampsia through bioinformatics and machine learning methods.

Weiwen Li · Lijun Zhong · Kewen Zhao · Jincheng Xie · Shaodong Deng · Yunyong Fang

BMC pregnancy and childbirth · 2025 doi:10.1186/s12884-025-07257-0

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:39934690
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2026-11-01T20:30:12Z
updated_at
2026-11-01T22:13:38Z
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paper object · 10 fields
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title
Identification of critical biomarkers and immune infiltration in preeclampsia through bioinformatics and machine learning methods.
doi
10.1186/s12884-025-07257-0
pmid
39934690
authors array · 6 items
[0]
Weiwen Li
[1]
Lijun Zhong
[2]
Kewen Zhao
[3]
Jincheng Xie
[4]
Shaodong Deng
[5]
Yunyong Fang
journal
BMC pregnancy and childbirth
year
2025
abstract
BACKGROUND: Preeclampsia (PE) is a multisystem progressive disease that occurs during pregnancy. Previous studies have shown that the immune system is involved in the placental trophoblast function and the pathological process of uterine vascular remodeling in PE. However, its molecular mechanism is still unclear. This study aimed to identify critical genes and immune cells involved in the pathological process of PE. METHODS: The PE-related GSE74341 and GSE160888 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis were combined to screen the PE-related DEGs. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic specificity of obtained DEGs, and the GSE35574 dataset was used for preliminary validation. Furthermore, the single-sample Gene Set Enrichment Analysis (ssGSEA) was used to elucidate the correlation between the DEGs and the 28 types of infiltrating immune cells in PE. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to verify the differential expression of DEGs in the PE placental tissues. RESULTS: A total of 143 DEGs (DE-mRNAs) were screened using the PE datasets. The analysis of DEG modules and LASSO logistic regression were used to identify high-temperature requirement factor A4 (HtrA4), tumour suppressor candidate 3 (TUSC3), endothelial protein C receptor gene (PROCR), claudin 3 (CLDN3), and thioredoxin binding protein (TXNIP) as the hub DEGs in PE. Furthermore, validation with the GSE35574 dataset and ROC analysis was used to clarify that the HTRA4, PROCR, and TXNIP genes are potential markers of PE and are closely related to the infiltrating immune cells in PE, such as gamma delta T cells, mast cells, natural killer cells, and T follicular helper cells. Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001). CONCLUSION: HTRA4, PROCR, and TXNIP can be used as potential PE biomarkers to provide a new strategy for early diagnosing and treating PE.
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Differences between groups were analyzed with a t-test using SPSS 19.0, and graphs were plotted using GraphPad 6.0 software.
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Differences between groups were analyzed with a t-test using SPSS 19.0, and graphs were plotted using GraphPad 6.0 software.
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The datasets generated and analyzed during the current study are available in the Gene Expression Omnibus (GEO) database. (http://www.ncbi.nlm.nih.gov/geo/).
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Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001).
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Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001).
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Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001).
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Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001).
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RNA microarray analysis of human placenta in normal pregnancy and preeclampsia
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Differentially expressed microRNAs revealed by molecular signatures of Preeclampsia and IUGR in human placenta
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Gene expression profiling reveal different molecular pattern in G-protein coupled receptor protein signaling pathway between early- and late-onset preeclampsia
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39934690", "kind": "science-record", "revision": 3, "content_hash": "sha256:ad2ea67dd614370713843f1cb408db04ad4db2b12b3b572a4b2d295086f6cd7c", "created_at": "2026-11-01T20:30:12Z", "updated_at": "2026-11-01T22:13:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of critical biomarkers and immune infiltration in preeclampsia through bioinformatics and machine learning methods.", "doi": "10.1186/s12884-025-07257-0", "pmid": "39934690", "authors": ["Weiwen Li", "Lijun Zhong", "Kewen Zhao", "Jincheng Xie", "Shaodong Deng", "Yunyong Fang"], "journal": "BMC pregnancy and childbirth", "year": 2025, "abstract": "BACKGROUND: Preeclampsia (PE) is a multisystem progressive disease that occurs during pregnancy. Previous studies have shown that the immune system is involved in the placental trophoblast function and the pathological process of uterine vascular remodeling in PE. However, its molecular mechanism is still unclear. This study aimed to identify critical genes and immune cells involved in the pathological process of PE.\nMETHODS: The PE-related GSE74341 and GSE160888 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis were combined to screen the PE-related DEGs. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic specificity of obtained DEGs, and the GSE35574 dataset was used for preliminary validation. Furthermore, the single-sample Gene Set Enrichment Analysis (ssGSEA) was used to elucidate the correlation between the DEGs and the 28 types of infiltrating immune cells in PE. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to verify the differential expression of DEGs in the PE placental tissues.\nRESULTS: A total of 143 DEGs (DE-mRNAs) were screened using the PE datasets. The analysis of DEG modules and LASSO logistic regression were used to identify high-temperature requirement factor A4 (HtrA4), tumour suppressor candidate 3 (TUSC3), endothelial protein C receptor gene (PROCR), claudin 3 (CLDN3), and thioredoxin binding protein (TXNIP) as the hub DEGs in PE. Furthermore, validation with the GSE35574 dataset and ROC analysis was used to clarify that the HTRA4, PROCR, and TXNIP genes are potential markers of PE and are closely related to the infiltrating immune cells in PE, such as gamma delta T cells, mast cells, natural killer cells, and T follicular helper cells. Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001).\nCONCLUSION: HTRA4, PROCR, and TXNIP can be used as potential PE biomarkers to provide a new strategy for early diagnosing and treating PE.", "claims": [{"id": "claim-method", "statement": "Differences between groups were analyzed with a t-test using SPSS 19.0, and graphs were plotted using GraphPad 6.0 software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39934690", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "Differences between groups were analyzed with a t-test using SPSS 19.0, and graphs were plotted using GraphPad 6.0 software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and analyzed during the current study are available in the Gene Expression Omnibus (GEO) database. (http://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39934690", "locator": "sections[26] \"notes\" paragraph 1", "quote": "The datasets generated and analyzed during the current study are available in the Gene Expression Omnibus (GEO) database. (http://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001).", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001)."}, "evidence": [{"asset": "source:pmid:39934690", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues (p < 0.001).", "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:39934690"], "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:GSE160888"], "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:GSE160888"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39934690", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12884-025-07257-0", "sha256": "sha256:c89efaa86fdc28d946dbe23c8f61a47b1c5712a937adaeb820acb09bf61ed875", "bytes": 26755, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12884-025-07257-0", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11817261", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE160888", "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=GSE160888", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE160888", "version": null, "note": "The datasets generated and analyzed during the current study are available in the Gene Expression Omnibus (GEO) database. 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