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pmid:36226177
A nine-consensus-prognostic -gene-based prognostic signature, recognizing the dichotomized subgroups of gastric cancer patients with different clinical outcomes and therapeutic strategies.
Dan Ji · Yang Yang · Fei Zhou · Chao Li
Frontiers in genetics · 2022 doi:10.3389/fgene.2022.909175
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Experiment
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Complete file
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Methods and materials: A total of 921 GC patients from three GEO cohorts were enrolled in the current study. The GSE15459 and GSE62254 cohorts were used to select the top prognostic gene via the evaluation of the area under the receiver operating characteristic (ROC) curve (AUC) values. The GSE84437 cohort was used as the external validation cohort. Least absolute shrinkage and selector operation (LASSO) regression analysis was applied to reduce the feature dimension and construct the prognostic signature. Furthermore, a nomogram was constructed by integrating the independent prognostic analysis and validated by calibration plot, decision curve analysis and clinical impact curve. The molecular features and response to chemo-/immunotherapy among risk subgroups were evaluated by the \"MOVICS\" and \"ESTAMATE\" R packages and the SubMap algorithm. Lauren classification and ACRG molecular subtype were obtained to compare with the risk model. Results: Forty-four prognosis-associated genes were identified with a preset cutoff AUC value of 0.65 in both the GSE62254 and GSE15459 cohorts. With the 10-fold cross validation analysis of LASSO, nine genes were selected to construct the nine-consensus-prognostic-gene signature. The signature showed good prognostic value in the GSE62254 (p < 0.001, HR: 3.81, 95% CI: 2.44-5.956) and GSE15459 (p < 0.001, HR: 2.65, 95% CI: 1.892-3.709) cohorts and the external validation GSE84437 cohort (p < 0.001, HR: 2.06, 95% CI: 1.554-2.735). The nomogram constructed based on two independent predictive factors, tumor stage and the signature, predicted events tightly consistent with the actual (Hosmer-Lemeshow p value: 1-year, 0.624; 3-years, 0.795; 5-years, 0.824). For the molecular features, we observed the activation of apical junction, epithelial mesenchymal transition, and immune pathways in the high-risk group, while in the low-risk group, cell cycle associated G2M, E2F and MYC target pathways were activated. Based on the results we obtained, we indicated that gastric patients in the low-risk group are more suitable for 5-fluorouracil therapy, while high-risk group patients are more suitable for anti-CTLA4 immunotherapy, these results need more support in the further studies. After compare with proposed molecular subtypes, we realized that the nine-consensus prognostic gene signature is a powerful addition to identify the gastric patients with poor prognosis. Conclusion: In summary, we constructed a robust nine-consensus-prognostic-gene signature for the prediction of GC prognosis, which can also predict the personalized treatment of GC patients.", "claims": [{"id": "claim-method", "statement": "Least absolute shrinkage and selector operation (LASSO) regression analysis was applied to reduce the feature dimension and construct the prognostic signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36226177", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Least absolute shrinkage and selector operation (LASSO) regression analysis was applied to reduce the feature dimension and construct the prognostic signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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"sample_count": 483, "group_sizes": null, "group_sizes_basis": null, "platform": "6947", "taxon": "Homo sapiens", "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:GSE15459 not downloaded", "asset:data:geo:GSE15459 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": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {"hazard_ratio": "and log-rank test, and hazard ratio (HR) and 95% confidence", "confidence_interval": "zard ratio (HR) and 95% 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{}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-4", "family": "model_calibration", "specific": "decision_curve", "label": "Model calibration / clinical utility", "dsl_operations": ["calibration_bins", "net_benefit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictions_and_outcomes"], "evidence": {"score": 0.7, "band": "medium", "quote": "decision curve analysis"}}, {"id": "method-5", "family": null, "specific": null, "label": "Least absolute shrinkage and selector operation (LASSO) regression analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Least absolute shrinkage and selector operation (LASSO) regression analysis was applied to reduce the feature dimension and construct the prognostic signature."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "calibration_bins", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "calibration_bins", "expected_value": 0.001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_named_unmapped"]}, "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE62254", "GSE15459", "GSE84437"], "resolved_accessions": ["GSE62254", "GSE15459", "GSE84437"], "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 GSE62254, GSE15459, GSE84437 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:36226177", "data:geo:GSE15459"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE15459"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:10:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16610, "completion_tokens": 1949, "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:36226177", "type": "paper", "label": "pmid:36226177"}, {"id": "source:pmid:36226177", "type": "manuscript", "label": "PMID 36226177 full text"}, {"id": "data:geo:GSE15459", "type": "dataset", "label": "GEO GSE15459"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36226177", "type": "paper", "label": "pmid:36226177"}, {"id": "source:pmid:36226177", "type": "manuscript", "label": "PMID 36226177 full text"}, {"id": "data:geo:GSE15459", "type": "dataset", "label": "GEO GSE15459"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36226177", "type": "extraction", "used": ["source:pmid:36226177"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE15459", "type": "accession_resolution", "used": ["data:geo:GSE15459"], "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:36226177", "parent_hash": "sha256:5972fc019408147bca0ae3b69523582801fce86cee0cdf9670663c29a0db7cad", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE15459 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", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Cox regression"], "order_basis": "analysis_only", "id": "assay:1"}]}