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pmid:40735606

Analysis and validation of necroptosis-related diagnostic biomarkers associated with immune infiltration in bronchopulmonary dysplasia.

Haixia Tu · Changjiang Fang · Ping Gan · Yunyun Gu · Nana Peng · Honghua Jiang · Weiwei Hou · Guihua Shu

Frontiers in pediatrics · 2025 doi:10.3389/fped.2025.1578628

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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pmid:40735606
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title
Analysis and validation of necroptosis-related diagnostic biomarkers associated with immune infiltration in bronchopulmonary dysplasia.
doi
10.3389/fped.2025.1578628
pmid
40735606
authors array · 8 items
[0]
Haixia Tu
[1]
Changjiang Fang
[2]
Ping Gan
[3]
Yunyun Gu
[4]
Nana Peng
[5]
Honghua Jiang
[6]
Weiwei Hou
[7]
Guihua Shu
journal
Frontiers in pediatrics
year
2025
abstract
Background: Bronchopulmonary dysplasia (BPD) is the most common serious complication in very preterm infants. This study aims to identify necroptosis-related genes (NRGs) and analyze the relationship between necroptosis-related diagnostic markers and immune infiltration in BPD. Methods: We obtained the dataset GSE32472 from the GEO database and analyzed the differentially expressed NRGs (DE-NRGs). We identified the biological functions and pathways of DE-NRGs. RF (random forest) and LASSO (least absolute shrinkage and selection operator) algorithms were applied to identify hub genes. We explored the immune landscape of BPD and controls by CIBERSORT. The correlations between hub genes and immune cells were evaluated using Spearman correlation analysis. ELISA was used to verify the diagnostic value of hub genes in patients with BPD in our hospital. Results: 27 DE-NRGs were screened. We found the primary biological functions and pathways of DE-NRGs, including necroptosis, and regulation of inflammatory response. Three hub genes (PELI1, PYGL, and STAT4) were identified and utilized to construct a diagnostic nomogram. The AUC value of the nomogram was greater than 0.7 in the validation dataset GSE188944. CIBERSORT showed that the proportions of 6 different immune cell types in the BPD group were higher or lower than the control group (P < 0.05). Correlation analysis showed that three hub genes may correlate with immune cells to varying degrees. Serum ELISA results of PELI1 and PYGL showed no significant difference between BPD and Controls (P > 0.05), the expression level of STAT4 was downregulated in BPD samples (P < 0.05), and the AUC value of the STAT4 was higher than 0.7. Conclusion: The necroptosis-related gene STAT4 can be a diagnostic marker of BPD patients. The necroptosis-related gene and immune infiltration may be related to the progression of BPD.
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ROC (receiver operating characteristic) curves were used to assess the diagnostic value of hub genes in BPD, and ROC curve analysis was conducted with the “pROC” R package.
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ROC (receiver operating characteristic) curves were used to assess the diagnostic value of hub genes in BPD, and ROC curve analysis was conducted with the “pROC” R package.
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The necroptosis-related gene STAT4 can be a diagnostic marker of BPD patients.
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The paper names GSE32472, GSE188944 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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aluated using Spearman correlation analysis. ELISA was used to verify the diagnostic value of h
[1]
with immune cells to varying degrees. Serum ELISA results of PELI1 and PYGL showed no signific
[2]
The human enzyme-linked immunosorbent assay (ELISA) kits (PELI1, PYGL, and STAT4) were purchase
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GL, and STAT4 in serum were determined using ELISA. The experimental procedures were conducted
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40735606", "kind": "science-record", "revision": 3, "content_hash": "sha256:cd0df048549b1a0266c01fccc0e491b4f4dcebe8ead2fa08dbc7c50424dd6d0f", "created_at": "2026-11-01T20:30:50Z", "updated_at": "2026-11-01T22:14:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis and validation of necroptosis-related diagnostic biomarkers associated with immune infiltration in bronchopulmonary dysplasia.", "doi": "10.3389/fped.2025.1578628", "pmid": "40735606", "authors": ["Haixia Tu", "Changjiang Fang", "Ping Gan", "Yunyun Gu", "Nana Peng", "Honghua Jiang", "Weiwei Hou", "Guihua Shu"], "journal": "Frontiers in pediatrics", "year": 2025, "abstract": "Background: Bronchopulmonary dysplasia (BPD) is the most common serious complication in very preterm infants. This study aims to identify necroptosis-related genes (NRGs) and analyze the relationship between necroptosis-related diagnostic markers and immune infiltration in BPD.\nMethods: We obtained the dataset GSE32472 from the GEO database and analyzed the differentially expressed NRGs (DE-NRGs). We identified the biological functions and pathways of DE-NRGs. RF (random forest) and LASSO (least absolute shrinkage and selection operator) algorithms were applied to identify hub genes. We explored the immune landscape of BPD and controls by CIBERSORT. The correlations between hub genes and immune cells were evaluated using Spearman correlation analysis. ELISA was used to verify the diagnostic value of hub genes in patients with BPD in our hospital.\nResults: 27 DE-NRGs were screened. We found the primary biological functions and pathways of DE-NRGs, including necroptosis, and regulation of inflammatory response. Three hub genes (PELI1, PYGL, and STAT4) were identified and utilized to construct a diagnostic nomogram. The AUC value of the nomogram was greater than 0.7 in the validation dataset GSE188944. CIBERSORT showed that the proportions of 6 different immune cell types in the BPD group were higher or lower than the control group (P < 0.05). Correlation analysis showed that three hub genes may correlate with immune cells to varying degrees. Serum ELISA results of PELI1 and PYGL showed no significant difference between BPD and Controls (P > 0.05), the expression level of STAT4 was downregulated in BPD samples (P < 0.05), and the AUC value of the STAT4 was higher than 0.7.\nConclusion: The necroptosis-related gene STAT4 can be a diagnostic marker of BPD patients. The necroptosis-related gene and immune infiltration may be related to the progression of BPD.", "claims": [{"id": "claim-method", "statement": "ROC (receiver operating characteristic) curves were used to assess the diagnostic value of hub genes in BPD, and ROC curve analysis was conducted with the “pROC” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40735606", "locator": "sections[7] \"Diagnostic value of hub genes on the 5th, and 14th days of life\" paragraph 2", "quote": "ROC (receiver operating characteristic) curves were used to assess the diagnostic value of hub genes in BPD, and ROC curve analysis was conducted with the “pROC” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40735606", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The necroptosis-related gene STAT4 can be a diagnostic marker of BPD patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40735606", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The necroptosis-related gene STAT4 can be a diagnostic marker of BPD patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The necroptosis-related gene STAT4 can be a diagnostic marker of BPD patients.", "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:40735606"], "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:GSE188944"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE188944"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40735606", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fped.2025.1578628", "sha256": "sha256:4c08d4700abc7e797715ccc7ac9531ae717ce52a7f1c0e87269896d25893f919", "bytes": 28008, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fped.2025.1578628", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12303952", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE188944", "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=GSE188944", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE188944", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE32472", "GSE188944"], "resolved_accessions": ["GSE32472", "GSE188944"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE32472, GSE188944 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": [], "assets": ["source:pmid:40735606", "data:geo:GSE188944"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE188944"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:58:17Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8623, "completion_tokens": 1384, "cached_tokens": 256}}, "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:40735606", "type": "paper", "label": "pmid:40735606"}, {"id": "source:pmid:40735606", "type": "manuscript", "label": "PMID 40735606 full text"}, {"id": "data:geo:GSE188944", "type": "dataset", "label": "GEO GSE188944"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40735606", "type": "paper", "label": "pmid:40735606"}, {"id": "source:pmid:40735606", "type": "manuscript", "label": "PMID 40735606 full text"}, {"id": "data:geo:GSE188944", "type": "dataset", "label": "GEO GSE188944"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40735606", "type": "extraction", "used": ["source:pmid:40735606"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE188944", "type": "accession_resolution", "used": ["data:geo:GSE188944"], "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:40735606", "parent_hash": "sha256:d7fff1dbe762acfc24ce5c3d5798d529a99b164064a8508a52b0e79f4f77aeab", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE188944 licence not read", "asset:data:geo:GSE188944 not downloaded", "asset:data:geo:GSE32472 licence not read", "asset:data:geo:GSE32472 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["aluated using Spearman correlation analysis. ELISA was used to verify the diagnostic value of h", "with immune cells to varying degrees. Serum ELISA results of PELI1 and PYGL showed no signific", "The human enzyme-linked immunosorbent assay (ELISA) kits (PELI1, PYGL, and STAT4) were purchase", "GL, and STAT4 in serum were determined using ELISA. The experimental procedures were conducted"], "order_basis": "paper_text_order:853", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student's t-test"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}