A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35141229", "kind": "science-record", "revision": 5, "content_hash": "sha256:9bb904a6fd1a08ba95935687d6f5562de41ddddeec1ccb23fddd52d8d6cc09d3", "created_at": "2026-11-01T17:36:53Z", "updated_at": "2026-11-01T22:48:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma.", "doi": "10.3389/fcell.2021.758777", "pmid": "35141229", "authors": ["Wenhao Ouyang", "Yupeng Jiang", "Shiyi Bu", "Tiantian Tang", "Linjie Huang", "Ming Chen", "Yujie Tan", "Qiyun Ou", "Luhui Mao", "Yingjie Mai", "Herui Yao", "Yunfang Yu", "Xiaoling Lin"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is associated with poor prognosis. However, current stage-based clinical methods are insufficient for survival prediction and decision-making. This study aimed to establish a novel model for evaluating the risk of LUAD based on hypoxia, immunity, and epithelial-mesenchymal transition (EMT) gene signatures. Methods: In this study, we used data from TCGA-LUAD for the training cohort and GSE68465 and GSE72094 for the validation cohorts. Immunotherapy datasets GSE135222, GSE126044, and IMvigor210 were obtained from a previous study. Using bioinformatic and machine algorithms, we established a risk model based on hypoxia, immune, and EMT gene signatures, which was then used to divide patients into the high and low risk groups. We analyzed differences in enriched pathways between the two groups, following which we investigated whether the risk score was correlated with stemness scores, genes related to m6A, m5C, m1A and m7G modification, the immune microenvironment, immunotherapy response, and multiple anti-cancer drug sensitivity. Results: Overall survival differed significantly between the high-risk and low-risk groups (HR = 4.26). The AUCs for predicting 1-, 3-, and 5-year survival were 0.763, 0.766, and 0.728, respectively. In the GSE68465 dataset, the HR was 2.03, while the AUCs for predicting 1-, 3-, and 5-year survival were 0.69, 0.651, and 0.618, respectively. The corresponding values in the GSE72094 dataset were an HR of 2.36 and AUCs of 0.653, 0.662, and 0.749, respectively. The risk score model could independently predict OS in patients with LUAD, and highly correlated with stemness scores and numerous m6A, m5C, m1A and m7G modification-related genes. Furthermore, the risk model was significantly correlated with multiple immune microenvironment characteristics. In the GSE135222 dataset, the HR was 4.26 and the AUC was 0.702. Evaluation of the GSE126044 and IMvigor210 cohorts indicated that PD-1/PD-LI inhibitor treatment may be indicated in patients with low risk scores, while anti-cancer therapy with various drugs may be indicated in patients with high risk scores. Conclusion: Our novel risk model developed based on hypoxia, immune, and EMT gene signatures can aid in predicting clinical prognosis and guiding treatment in patients with LUAD.", "claims": [{"id": "claim-method", "statement": "DEGs were screened using the Wilcoxon test. Univariate Cox analysis of overall survival (OS) was performed to screen relevant genes with prognostic values. Kaplan–Meier survival curves were generated and compared between the two groups using the log-rank test. The associations between the risk score determined using the prognostic model and the stromal score, stemness score, and immune score were assessed using Spearman correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35141229", "locator": "sections[10] \"2.8 Statistical Analysis\" paragraph 2", "quote": "DEGs were screened using the Wilcoxon test. Univariate Cox analysis of overall survival (OS) was performed to screen relevant genes with prognostic values. Kaplan–Meier survival curves were generated and compared between the two groups using the log-rank test. The associations between the risk score determined using the prognostic model and the stromal score, stemness score, and immune score were assessed using Spearman correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "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.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35141229", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "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."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The 27-gene risk model significantly discriminated overall survival between high-risk and low-risk LUAD patients, with an HR of 4.26 and 1-, 3-, and 5-year survival AUCs of 0.763, 0.766, and 0.728, respectively.", "kind": "quantitative", "target": {"value": 4.26, "unit": "hazard ratio", "tolerance": null, "source": "Overall survival differed significantly between the high-risk and low-risk groups (HR = 4.26)."}, "evidence": [{"asset": "source:pmid:35141229", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Overall survival differed significantly between the high-risk and low-risk groups (HR = 4.26)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The 27-gene risk model significantly discriminated overall survival between high-risk and low-risk LUAD patients, with an HR of 4.26 and 1-, 3-, and 5-year survival AUCs of 0.763, 0.766, and 0.728, respectively.", "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:35141229"], "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:GSE126044"], "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:GSE126044"], "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:35141229", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.758777", "sha256": "sha256:4d12288468e039089ba994bd18bf06221b0e08311f99933ebdc69cc5fcff1a95", "bytes": 39602, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.758777", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8819669", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE126044", "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=GSE126044", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE126044", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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"asset:data:geo:GSE135222 licence not read", "asset:data:geo:GSE68465 not downloaded", "asset:data:geo:GSE68465 licence not read", "asset:data:geo:GSE72094 not downloaded", "asset:data:geo:GSE72094 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs were screened using the Wilcoxon test. Univariate Cox analysis of overall survival (OS) was performed to screen relevant genes with prognostic values. Kaplan–Meier survival curves were generated and compared between the two groups using the log-rank test. The associations between the risk score determined using the prognostic model and the stromal score, stemness score, and immune score were assessed using Spearman correlation analysis."}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-5", "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": 0.8, "band": "high", "quote": "GO enrichment"}}, {"id": "method-6", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC analysis"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "classification_metrics", "expected_value": 4.26, "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."}], "gaps": ["method.group_comparison_wilcoxon"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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", "GSE72094", "GSE135222", "GSE126044"], "resolved_accessions": ["GSE68465", "GSE72094", "GSE135222", "GSE126044"], "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 GSE68465, GSE72094, GSE135222, GSE126044 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": [], "assets": ["source:pmid:35141229", "data:geo:GSE126044"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE126044"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:33:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11771, "completion_tokens": 2264, "cached_tokens": 188}}, "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:35141229", "type": "paper", "label": "pmid:35141229"}, {"id": "source:pmid:35141229", "type": "manuscript", "label": "PMID 35141229 full text"}, {"id": "data:geo:GSE126044", "type": "dataset", "label": "GEO GSE126044"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35141229", "type": "paper", "label": "pmid:35141229"}, {"id": "source:pmid:35141229", "type": "manuscript", "label": "PMID 35141229 full text"}, {"id": "data:geo:GSE126044", "type": "dataset", "label": "GEO GSE126044"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35141229", "type": "extraction", "used": ["source:pmid:35141229"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE126044", "type": "accession_resolution", "used": ["data:geo:GSE126044"], "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:35141229", "parent_hash": "sha256:5209cb6a270e4bef58ab8c40b31a8c8032890d3ba55df4fd50ef4a842f2ced07", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE126044 licence not read", "asset:data:geo:GSE126044 not downloaded", "asset:data:geo:GSE135222 licence not read", "asset:data:geo:GSE135222 not downloaded", "asset:data:geo:GSE68465 licence not read", "asset:data:geo:GSE68465 not downloaded", "asset:data:geo:GSE72094 licence not read", "asset:data:geo:GSE72094 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "methylation_array", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["RSORT, CIBERSORT-ABS, XCELL, MCPCOUNTER, and EPIC algorithms. The “gsva” R package was used to", "CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, EPIC algorithms among high risk score group and l"], "order_basis": "paper_text_order:2860", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["DEGs were screened using the Wilcoxon test. Univariate Cox analysis of overall survival (OS) was performed to screen relevant genes with prognostic values. Kaplan–Meier survival curves were generated and compared between the two groups using the log-rank test. The associations between the risk score determined using the prognostic model and the stromal score, stemness score, and immune score were assessed using Spearman correlation analysis."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}