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pmid:39636505
Identification of common core genes and pathways in childhood sepsis and cancer by bioinformatics analysis.
Yi-Ran He · Ni Ding · Ming-Chen Han · Hong-Yu He · Li-Zhen Xuan · Zhun-Yong Gu · Ming Zhong · Min-Jie Ju
Discover oncology · 2024 doi:10.1007/s12672-024-01651-4
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Experiment
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Complete file
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Some studies have suggested a possible association between sepsis and cancer; however, few have investigated the core genes involved in both diseases.\nMETHODS: Core genes common to both sepsis and cancer were identified using pediatric sepsis datasets (GEO: GSE26378, GSE4607, GSE8121 and GSE13904) and cancer databases (TCGA: BRCA, COADREAD, ESCA, KIRC, LIHC, LUAD, STAD). Gene Ontology (GO) and Reactome enrichment analyses, along with a protein-protein interaction (PPI) network analysis, were performed. Pharmacophore screening was applied to predict the targets of oxymatrine and ulinastatin, and potential target genes shared by both cancer and sepsis were identified. Survival analysis was performed. The association between the target genes and tumor size and number of positive lymph nodes was investigated by Pearson correlation analysis. The association between the target genes and tumor stage was investigated by Fisher's exact test. Molecular docking analysis was performed to evaluate the affinity of the candidate drugs for their targets.\nRESULTS: A total of 641 common genes were identified. GO enrichment analysis showed that common genes were enriched in neutrophil degranulation, inflammatory response and innate immune response. Reactome enrichment analysis showed that common genes were enriched in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, transcriptional regulation of granulopoiesis and interleukin-10 signaling. The PPI network showed that the top 10 core genes were TLR4, IL1B, IL10, ITGAM, TLR2, PTPRC, CDK1, FOS, MMP9 and ITGB2. The survival analysis showed that the high expression of BCAT1, CSAD, G6PD, GM2A, MMP9, PYGL and TOP2A was associated with poorer prognosis in several cancers. Molecular docking showed that oxymatrine and ulinastatin can bind to protein targets with highly stable binding.\nCONCLUSIONS: We identified genes with common effects on both childhood sepsis and cancer, which provides new insights into the association between sepsis and cancer. In addition, two drugs with potential clinical application value were identified. Further studies are required to validate the role of these common core genes in sepsis and cancer and to evaluate the potential utility of these drugs.", "claims": [{"id": "claim-method", "statement": "In the GEO database, the gene fold difference (FC) was calculated based on the normalized signal value of the chip, the significant p value was obtained by T test, and the p value was corrected by the BH method to obtain the FDR. The screening criteria for differential genes were FC > 2 and FDR < 0.05. In the TCGA database, based on the downloaded count data, DESeq2 was used to calculate the genetic differences between groups, the negative biphasic distribution test was used to obtain a significant p value, and the p value was corrected by the BH method to obtain FDR. The screening criteria for differential genes were FC > 2 and FDR < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39636505", "locator": "sections[5] \"Differential expression analysis\" paragraph 2", "quote": "In the GEO database, the gene fold difference (FC) was calculated based on the normalized signal value of the chip, the significant p value was obtained by T test, and the p value was corrected by the BH method to obtain the FDR. The screening criteria for differential genes were FC > 2 and FDR < 0.05. In the TCGA database, based on the downloaded count data, DESeq2 was used to calculate the genetic differences between groups, the negative biphasic distribution test was used to obtain a significant p value, and the p value was corrected by the BH method to obtain FDR. The screening criteria for differential genes were FC > 2 and FDR < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used in this study are all from public databases and can be obtained through the following websites. GSE26378: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26378; GSE4607: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4607; GSE8121: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8121; GSE13904: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13904; BRCA: https://portal.gdc.cancer.gov/projects/TCGA-BRCA; COADREAD: https://portal.gdc.cancer.gov/projects/TCGA-COAD; ESCA: https://portal.gdc.cancer.gov/projects/TCGA-ESCA; KIRC: https://portal.gdc.cancer.gov/projects/TCGA-KIRC; LIHC: https://portal.gdc.cancer.gov/projects/TCGA-LIHC; LUAD: https://portal.gdc.cancer.gov/projects/TCGA-LUAD; STAD: https://portal.gdc.cancer.gov/projects/TCGA-STAD; Oxymatrine structure file: https://pubchem.ncbi.nlm.nih.gov/compound/114850; Ulinastatin structure file: https://pubchem.ncbi.nlm.nih.gov/compound/105102.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39636505", "locator": "sections[24] \"notes\" paragraph 1", "quote": "The data used in this study are all from public databases and can be obtained through the following websites. GSE26378: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26378; GSE4607: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4607; GSE8121: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8121; GSE13904: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13904; BRCA: https://portal.gdc.cancer.gov/projects/TCGA-BRCA; COADREAD: https://portal.gdc.cancer.gov/projects/TCGA-COAD; ESCA: https://portal.gdc.cancer.gov/projects/TCGA-ESCA; KIRC: https://portal.gdc.cancer.gov/projects/TCGA-KIRC; LIHC: https://portal.gdc.cancer.gov/projects/TCGA-LIHC; LUAD: https://portal.gdc.cancer.gov/projects/TCGA-LUAD; STAD: https://portal.gdc.cancer.gov/projects/TCGA-STAD; Oxymatrine structure file: https://pubchem.ncbi.nlm.nih.gov/compound/114850; Ulinastatin structure file: https://pubchem.ncbi.nlm.nih.gov/compound/105102."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 641 common genes were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39636505", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 641 common genes were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 641 common genes were identified.", "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:39636505"], "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. 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The screening criteria for differential genes were FC > 2 and FDR < 0.05. In the TCGA database, based on the downloaded count data, DESeq2 was used to calculate the genetic differences between groups, the negative biphasic distribution test was used to obtain a significant p value, and the p value was corrected by the BH method to obtain FDR. The screening criteria for differential genes were FC > 2 and FDR < 0.05."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pearson correlation"}}, {"id": "method-3", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-4", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "GO enrichment"}}, {"id": "method-5", "family": "contingency_analysis", "specific": "fisher_exact", "label": "Categorical (contingency table) analysis", "dsl_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.7, "band": "medium", "quote": "Fisher's exact"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: deseq2."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE26378", "GSE4607", "GSE8121", "GSE13904"], "resolved_accessions": ["GSE26378", "GSE4607", "GSE8121", "GSE13904"], "statements": ["The data used in this study are all from public databases and can be obtained through the following websites. GSE26378: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26378; GSE4607: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4607; GSE8121: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8121; GSE13904: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13904; BRCA: https://portal.gdc.cancer.gov/projects/TCGA-BRCA; COADREAD: https://portal.gdc.cancer.gov/projects/TCGA-COAD; ESCA: https://portal.gdc.cancer.gov/projects/TCGA-ESCA; KIRC: https://portal.gdc.cancer.gov/projects/TCGA-KIRC; LIHC: https://portal.gdc.cancer.gov/projects/TCGA-LIHC; LUAD: https://portal.gdc.cancer.gov/projects/TCGA-LUAD; STAD: https://portal.gdc.cancer.gov/projects/TCGA-STAD; Oxymatrine structure file: https://pubchem.ncbi.nlm.nih.gov/compound/114850; Ulinastatin structure file: https://pubchem.ncbi.nlm.nih.gov/compound/105102."], "basis": "The paper names GSE26378, GSE4607, GSE8121, GSE13904 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:39636505", "data:geo:GSE13904"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13904"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:40:52Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8484, "completion_tokens": 3798, "cached_tokens": 264}}, "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:39636505", "type": "paper", "label": "pmid:39636505"}, {"id": "source:pmid:39636505", "type": "manuscript", "label": "PMID 39636505 full text"}, {"id": "data:geo:GSE13904", "type": "dataset", "label": "GEO GSE13904"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39636505", "type": "paper", "label": "pmid:39636505"}, {"id": "source:pmid:39636505", "type": "manuscript", "label": "PMID 39636505 full text"}, {"id": "data:geo:GSE13904", "type": "dataset", "label": "GEO GSE13904"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39636505", "type": "extraction", "used": ["source:pmid:39636505"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13904", "type": "accession_resolution", "used": ["data:geo:GSE13904"], "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:39636505", "parent_hash": "sha256:656e8f72a5a8d8c360158d50dd1fd7d90e97212376dfb09a1d72a63c519ba245", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE13904 licence not read", "asset:data:geo:GSE13904 not downloaded", "asset:data:geo:GSE26378 licence not read", "asset:data:geo:GSE26378 not downloaded", "asset:data:geo:GSE4607 licence not read", "asset:data:geo:GSE4607 not downloaded", "asset:data:geo:GSE8121 licence not read", "asset:data:geo:GSE8121 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["In the GEO database, the gene fold difference (FC) was calculated based on the normalized signal value of the chip, the significant p value was obtained by T test, and the p value was corrected by the BH method to obtain the FDR. The screening criteria for differential genes were FC > 2 and FDR < 0.05. In the TCGA database, based on the downloaded count data, DESeq2 was used to calculate the genetic differences between groups, the negative biphasic distribution test was used to obtain a significant p value, and the p value was corrected by the BH method to obtain FDR. The screening criteria for differential genes were FC > 2 and FDR < 0.05."], "order_basis": "analysis_only", "id": "assay:1"}]}