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pmid:36178365
Establishment and validation of individualized clinical prognostic markers for LUAD patients based on autophagy-related genes.
Yuchang Fei · Junyi Xu · Liping Ge · Luting Chen · Huan Yu · Lei Pan · Peifeng Chen
Aging · 2022 doi:10.18632/aging.204097
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Complete file
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Bioinformatics analysis was performed on lung adenocarcinoma (LUAD) datasets to establish a multi-autophagy gene model to predict patient prognosis. LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database as a training set to construct a LUAD prognostic model. According to the risk score, a Kaplan-Meier cumulative curve was plotted to evaluate the prognostic value. Furthermore, a nomogram was established to predict the three-year and five-year survival of patients with LUAD based on their prognostic characteristics. Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001). The Kaplan-Meier cumulative curve showed that low-risk patients had significantly better overall (P<0.0001). The validation dataset GSE68465 further confirmed the nomogram's robust ability to assess the prognosis of LUAD patients. A prognosis model of autophagy-related genes based on a LUAD dataset was constructed and exhibited diagnostic value in the prognosis of LUAD patients. Moreover, real-time qPCR confirmed the expression patterns of EIF2AK3 and ITGB1 in LUAD cell lines. Two key autophagy-related genes have been suggested as prognostic markers for lung adenocarcinoma.", "claims": [{"id": "claim-method", "statement": "The Multivariate Cox proportional-hazards model showed that risk score was an independent prognostic marker for LUAD (HR =3.30, 95%CI = 2.3-4.6, P< 0.0001) (Figure 7B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36178365", "locator": "sections[7] \"Autophagy-related genes as an independent prognostic factor for LUAD\" paragraph 2", "quote": "The Multivariate Cox proportional-hazards model showed that risk score was an independent prognostic marker for LUAD (HR =3.30, 95%CI = 2.3-4.6, P< 0.0001) (Figure 7B)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We obtained datasets from publicly available databases for this analysis. 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They can be found in the four documents of TCGA-LUAD Clinical Data, GEO68465 Clinical Data, Autophagy Genes, and RT-qPCR Data in the Supplementary Materials."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001)."}, "evidence": [{"asset": "source:pmid:36178365", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001).", "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:36178365"], "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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These data are available in the following databases: TCGA: https://portal.gdc.cancer.gov/; GEO: https://www.ncbi.nlm.nih.gov/geo/; HADb: http://www.autophagy.lu/autophagy.html.\n\nIn addition to the gene expression data of LUAD downloaded from the TCGA database, the original data in this manuscript also included clinical data of TCGA-LUAD, and clinical data of the GSE68465 dataset in the GEO database, collation of autophagy-related genes, and RT-qPCR data of EIF2AK3 and ITGB1. They can be found in the four documents of TCGA-LUAD Clinical Data, GEO68465 Clinical Data, Autophagy Genes, and RT-qPCR Data in the Supplementary Materials.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We obtained datasets from publicly available databases for this analysis. 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No tolerance is published because the paper states none."}, {"id": "target-published-estimate-hazard-ratio", "claim_id": "claim-target-result", "operation": "calibration_bins", "expected_value": 3.3, "unit": "hazard ratio", "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": 0.0001, "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": []}, "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": ["GSE68465"], "resolved_accessions": ["GSE68465"], "statements": ["We obtained datasets from publicly available databases for this analysis. These data are available in the following databases: TCGA: https://portal.gdc.cancer.gov/; GEO: https://www.ncbi.nlm.nih.gov/geo/; HADb: http://www.autophagy.lu/autophagy.html.\n\nIn addition to the gene expression data of LUAD downloaded from the TCGA database, the original data in this manuscript also included clinical data of TCGA-LUAD, and clinical data of the GSE68465 dataset in the GEO database, collation of autophagy-related genes, and RT-qPCR data of EIF2AK3 and ITGB1. They can be found in the four documents of TCGA-LUAD Clinical Data, GEO68465 Clinical Data, Autophagy Genes, and RT-qPCR Data in the Supplementary Materials."], "basis": "The paper names GSE68465 in Gene Expression Omnibus (GEO) database 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:36178365", "data:geo:GSE68465"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE68465"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:07:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10493, "completion_tokens": 2262, "cached_tokens": 265}}, "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:36178365", "type": "paper", "label": "pmid:36178365"}, {"id": "source:pmid:36178365", "type": "manuscript", "label": "PMID 36178365 full text"}, {"id": "data:geo:GSE68465", "type": "dataset", "label": "GEO GSE68465"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36178365", "type": "paper", "label": "pmid:36178365"}, {"id": "source:pmid:36178365", "type": "manuscript", "label": "PMID 36178365 full text"}, {"id": "data:geo:GSE68465", "type": "dataset", "label": "GEO GSE68465"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36178365", "type": "extraction", "used": ["source:pmid:36178365"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE68465", "type": "accession_resolution", "used": ["data:geo:GSE68465"], "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:36178365", "parent_hash": "sha256:f0a87d00c5207ca15cbd74ebfe01f7af147d468b1b6b5cc613aba849f902eb8e", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE68465 licence not read", "asset:data:geo:GSE68465 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["gnosis of LUAD patients. Moreover, real-time qPCR confirmed the expression patterns of EIF2AK3", "e, collation of autophagy-related genes, and RT-qPCR data of EIF2AK3 and ITGB1. They can be found", "collation of autophagy-related genes, and RT-qPCR data of EIF2AK3 and ITGB1. They can be found", "68465 Clinical Data, Autophagy Genes, and RT-qPCR Data in the Supplementary Materials. Supplem"], "order_basis": "paper_text_order:1394", "id": "assay:1"}, {"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": 1.0, "evidence": ["The Multivariate Cox proportional-hazards model showed that risk score was an independent prognostic marker for LUAD (HR =3.30, 95%CI = 2.3-4.6, P< 0.0001) (Figure 7B)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}