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pmid:38327406
Activated CD4 T cells/Tregs derived immune-metabolism signature provide precise prognosis assessment for gastric cancer and beneficial for treatment option.
Junyu Huo · Zhen Shang · Xinyi Fan · Peng Sun
Heliyon · 2024 doi:10.1016/j.heliyon.2024.e25463
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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Group A was defined as having activated CD4 T cells/Tregs >1, while group B was defined as having activated CD4 T cells/Tregs <1. To compare the overall survival (OS) of the two groups, the Kaplan-Meier survival analysis was employed. The R package 'limma' was used to identify the immune and metabolism related genes that were expressed differentially between the two groups, with a false discovery rate (FDR) less than 0.05. The risk score (RS) was constructed by combining univariate Cox regression analysis, LASSO penalized Cox regression analysis, and multivariate Cox regression analysis. The median RS was used to classify high-risk (HR) and low-risk (LR) groups.\nResults: A predicted unfavorable outcome of GC was observed when the ratio of activated CD4 T cells to Tregs was less than 1. Our proposed RS was utilized for prognostic risk categorization in ten distinct independent cohorts (TCGA-STAD, n = 371; GSE84437, n = 433; GSE26253, n = 432; GSE13861, n = 65; GSE15459, n = 192; GSE26899, n = 93; GSE26901, n = 109; GSE28541, n = 40; GSE34942, n = 56; GSE62254, n = 300) and exhibited exceptional precision. In terms of tumor microenvironment (TME) and treatment strategies, compared to the LR group, the HR group was characterized by a higher infiltration levels of stromal cells, Tregs, macrophages, Tfh, mast cells, and NK cells, inclined to activated CD4 T cells/Tregs <1, and exhibited insensitivity to immunotherapy and multiple chemotherapy drugs. In relation to the potential molecular mechanism, the excessive activation of oncogenic pathways such as MAPK, hedgehog, WNT, calcium, and TGF-β signaling pathways may accelerate the malignant progression of GC by stimulating angiogenesis, promoting EMT, and altering ECM. Conversely, the overactivation of the P53 pathway is likely to inhibit tumor proliferation by regulating the cell cycle.\nConclusion: The immune-metabolism signature associated with the ratio of activated CD4 T cells and Tregs could be used to assess prognosis, TME, and treatment strategies in GC patients.", "claims": [{"id": "claim-method", "statement": "To compare the overall survival (OS) of the two groups, the Kaplan-Meier survival analysis was employed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38327406", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "To compare the overall survival (OS) of the two groups, the Kaplan-Meier survival analysis was employed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed for this study were obtained from The Cancer Genome Atlas (TCGA,https://portal.gdc.cancer.gov/), Gene Expression Omnibus(GEO, https:// www.ncbi.nlm.nih.gov/geo/), and The Cancer Immunome Atlas(TCIA, https://tcia.at/home).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38327406", "locator": "sections[22] \"Availability of data and material\" paragraph 2", "quote": "The datasets analysed for this study were obtained from The Cancer Genome Atlas (TCGA,https://portal.gdc.cancer.gov/), Gene Expression Omnibus(GEO, https:// www.ncbi.nlm.nih.gov/geo/), and The Cancer Immunome Atlas(TCIA, https://tcia.at/home)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The immune-metabolism signature associated with the ratio of activated CD4 T cells and Tregs could be used to assess prognosis, TME, and treatment strategies in GC patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38327406", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The immune-metabolism signature associated with the ratio of activated CD4 T cells and Tregs could be used to assess prognosis, TME, and treatment strategies in GC patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The immune-metabolism signature associated with the ratio of activated CD4 T cells and Tregs could be used to assess prognosis, TME, and treatment strategies in GC 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:38327406"], "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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"title": "Molecular subtypes in gastric cancer.", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE13861 not downloaded", "asset:data:geo:GSE13861 licence not read", "asset:data:geo:GSE15459 not downloaded", "asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE26253 not downloaded", "asset:data:geo:GSE26253 licence not read", "asset:data:geo:GSE26899 not downloaded", "asset:data:geo:GSE26899 licence not read", "asset:data:geo:GSE26901 not downloaded", "asset:data:geo:GSE26901 licence not read", "asset:data:geo:GSE28541 not downloaded", "asset:data:geo:GSE28541 licence not read", "asset:data:geo:GSE34942 not downloaded", "asset:data:geo:GSE34942 licence not read", "asset:data:geo:GSE62254 not downloaded", "asset:data:geo:GSE62254 licence not read", "asset:data:geo:GSE84437 not downloaded", "asset:data:geo:GSE84437 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To compare the overall survival (OS) of the two groups, the Kaplan-Meier survival analysis was employed."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-3", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"fdr_threshold": "the two groups, with a false discovery rate (FDR) less than 0"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "limma"}}], "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE84437", "GSE26253", "GSE13861", "GSE15459", "GSE26899", "GSE26901", "GSE28541", "GSE34942", "GSE62254"], "resolved_accessions": ["GSE84437", "GSE26253", "GSE13861", "GSE15459", "GSE26899", "GSE26901", "GSE28541", "GSE34942", "GSE62254"], "statements": ["The datasets analysed for this study were obtained from The Cancer Genome Atlas (TCGA,https://portal.gdc.cancer.gov/), Gene Expression Omnibus(GEO, https:// www.ncbi.nlm.nih.gov/geo/), and The Cancer Immunome Atlas(TCIA, https://tcia.at/home)."], "basis": "The paper names GSE84437, GSE26253, GSE13861, GSE15459, GSE26899, GSE26901, GSE28541, GSE34942, GSE62254 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:38327406", "data:geo:GSE13861"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13861"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:08:10Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10601, "completion_tokens": 2573, "cached_tokens": 128}}, "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:38327406", "type": "paper", "label": "pmid:38327406"}, {"id": "source:pmid:38327406", "type": "manuscript", "label": "PMID 38327406 full text"}, {"id": "data:geo:GSE13861", "type": "dataset", "label": "GEO GSE13861"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38327406", "type": "paper", "label": "pmid:38327406"}, {"id": "source:pmid:38327406", "type": "manuscript", "label": "PMID 38327406 full text"}, {"id": "data:geo:GSE13861", "type": "dataset", "label": "GEO GSE13861"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38327406", "type": "extraction", "used": ["source:pmid:38327406"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13861", "type": "accession_resolution", "used": ["data:geo:GSE13861"], "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:38327406", "parent_hash": "sha256:460599ce7769ddb624fa30c750333d8f5a97f4da1e4e45e4ddaf680e2f1f07a6", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE13861 licence not read", "asset:data:geo:GSE13861 not downloaded", "asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE15459 not downloaded", "asset:data:geo:GSE26253 licence not read", "asset:data:geo:GSE26253 not downloaded", "asset:data:geo:GSE26899 licence not read", "asset:data:geo:GSE26899 not downloaded", "asset:data:geo:GSE26901 licence not read", "asset:data:geo:GSE26901 not downloaded", "asset:data:geo:GSE28541 licence not read", "asset:data:geo:GSE28541 not downloaded", "asset:data:geo:GSE34942 licence not read", "asset:data:geo:GSE34942 not downloaded", "asset:data:geo:GSE62254 licence not read", "asset:data:geo:GSE62254 not downloaded", "asset:data:geo:GSE84437 licence not read", "asset:data:geo:GSE84437 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To compare the overall survival (OS) of the two groups, the Kaplan-Meier survival analysis was employed."], "order_basis": "analysis_only", "id": "assay:1"}]}