Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34869590", "kind": "science-record", "revision": 3, "content_hash": "sha256:fd87a39969bd9617dae586b5bb730918e3dfab9fe691efc4e7bdee22cf09461a", "created_at": "2026-11-01T17:36:35Z", "updated_at": "2026-11-01T21:26:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma.", "doi": "10.3389/fmolb.2021.757421", "pmid": "34869590", "authors": ["Zili Dai", "Taisheng Liu", "Guihong Liu", "Zhen Deng", "Peng Yu", "Baiyao Wang", "Bohong Cen", "Liyi Guo", "Jian Zhang"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear. Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration. Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME. Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.", "claims": [{"id": "claim-method", "statement": "Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34869590", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34869590", "locator": "sections[17] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001).", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001)."}, "evidence": [{"asset": "source:pmid:34869590", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (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:34869590"], "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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