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pmid:38948198

Suppression of P53 Pathway is an Important Factor Inducing Acute Graft-versus-Host Disease Through T Cell Activation Based on Bioinformatics Analysis.

Shiyu Wang · Wei Qin · Tingting Cheng · Cong Zeng · Xu Chen · Yajing Xu

Journal of inflammation research · 2024 doi:10.2147/JIR.S458860

Paper

complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:38948198
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title
Suppression of P53 Pathway is an Important Factor Inducing Acute Graft-versus-Host Disease Through T Cell Activation Based on Bioinformatics Analysis.
doi
10.2147/JIR.S458860
pmid
38948198
authors array · 6 items
[0]
Shiyu Wang
[1]
Wei Qin
[2]
Tingting Cheng
[3]
Cong Zeng
[4]
Xu Chen
[5]
Yajing Xu
journal
Journal of inflammation research
year
2024
abstract
Purpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question. Patients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort. Results: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis. Conclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.
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Initially, we applied gene set enrichment analysis (GSEA) to investigate the discrepancy of biological signaling pathway in T cells between aGVHD patients and non-aGVHD group.
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sections[11] "P53 Pathway is Suppressed in T Cells from aGVHD Patients" paragraph 2
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Initially, we applied gene set enrichment analysis (GSEA) to investigate the discrepancy of biological signaling pathway in T cells between aGVHD patients and non-aGVHD group.
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Publicly available datasets (GSE73809 and GSE4624) were analyzed in this study. These data can be found here: [GEO, https://www.ncbi.nlm.nih.gov/geo/].
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P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways.
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P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways.
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P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38948198", "kind": "science-record", "revision": 3, "content_hash": "sha256:e8d7aaa197a5a4a140ebace538167600e8a1b35bb188bc66ad0cd86142e928ea", "created_at": "2026-11-01T20:29:01Z", "updated_at": "2026-11-01T22:12:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Suppression of P53 Pathway is an Important Factor Inducing Acute Graft-versus-Host Disease Through T Cell Activation Based on Bioinformatics Analysis.", "doi": "10.2147/JIR.S458860", "pmid": "38948198", "authors": ["Shiyu Wang", "Wei Qin", "Tingting Cheng", "Cong Zeng", "Xu Chen", "Yajing Xu"], "journal": "Journal of inflammation research", "year": 2024, "abstract": "Purpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question.\nPatients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort.\nResults: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis.\nConclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.", "claims": [{"id": "claim-method", "statement": "Initially, we applied gene set enrichment analysis (GSEA) to investigate the discrepancy of biological signaling pathway in T cells between aGVHD patients and non-aGVHD group.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38948198", "locator": "sections[11] \"P53 Pathway is Suppressed in T Cells from aGVHD Patients\" paragraph 2", "quote": "Initially, we applied gene set enrichment analysis (GSEA) to investigate the discrepancy of biological signaling pathway in T cells between aGVHD patients and non-aGVHD group."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets (GSE73809 and GSE4624) were analyzed in this study. These data can be found here: [GEO, https://www.ncbi.nlm.nih.gov/geo/].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38948198", "locator": "sections[19] \"Data Sharing Statement\" paragraph 2", "quote": "Publicly available datasets (GSE73809 and GSE4624) were analyzed in this study. These data can be found here: [GEO, https://www.ncbi.nlm.nih.gov/geo/]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38948198", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways.", "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:38948198"], "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:GSE4624"], "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:group_comparison_wilcoxon", "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:GSE4624"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38948198", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/JIR.S458860", "sha256": "sha256:12c38398b9dedc6f9f30d243bfb0a7d1b8c419651ebda9038816d116166f9319", "bytes": 36454, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/JIR.S458860", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11214571", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE4624", "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=GSE4624", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE4624", "version": null, "note": "Publicly available datasets (GSE73809 and GSE4624) were analyzed in this study. 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