Identification of prognostic gene signature associated with microenvironment of lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31803536", "kind": "science-record", "revision": 7, "content_hash": "sha256:d29286c66d227f6da78c70fab093ca243355e7e6d348f29662333e4c5af2f53f", "created_at": "2026-11-01T15:40:52Z", "updated_at": "2026-11-01T22:01:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of prognostic gene signature associated with microenvironment of lung adenocarcinoma.", "doi": "10.7717/peerj.8128", "pmid": "31803536", "authors": ["Cheng Yue", "Hongtao Ma", "Yubai Zhou"], "journal": "PeerJ", "year": 2019, "abstract": "BACKGROUND: Lung cancer has the highest morbidity and mortality worldwide, and lung adenocarcinoma (LADC) is the most common pathological subtype. Accumulating evidence suggests the tumor microenvironment (TME) is correlated with the tumor progress and the patient's outcome. As the major components of TME, the tumor-infiltrated immune cells and stromal cells have attracted more and more attention. In this study, differentially expressed immune and stromal signature genes were used to construct a TME-related prognostic model for predicting the outcomes of LADC patients.\nMETHODS: The expression profiles of LADC samples with clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) related to the TME of LADC were identified using TCGA dataset by Wilcoxon rank sum test. The prognostic effects of TME-related DEGs were analyzed using univariate Cox regression. Then, the least absolute shrinkage and selection operator (LASSO) regression was performed to reduce the overfit and the number of genes for further analysis. Next, the prognostic model was constructed by step multivariate Cox regression and risk score of each sample was calculated. Then, survival and Receiver Operating Characteristic (ROC) analyses were conducted to validate the model using TCGA and GEO datasets, respectively. The Kyoto Encyclopedia of Genes and Genomes analysis of gene signature was performed using Gene Set Enrichment Analysis (GSEA). Finally, the overall immune status, tumor purity and the expression profiles of HLA genes of high- and low-risk samples was further analyzed to reveal the potential mechanisms of prognostic effects of the model.\nRESULTS: A total of 93 TME-related DEGs were identified, of which 23 DEGs were up-regulated and 70 DEGs were down-regulated. The univariate cox analysis indicated that 23 DEGs has the prognostic effects, the hazard ratio ranged from 0.65 to 1.25 (p < 0.05). Then, seven genes were screened out from the 23 DEGs by LASSO regression method and were further analyzed by step multivariate Cox regression. Finally, a three-gene (ADAM12, Bruton Tyrosine Kinase (BTK), ERG) signature was constructed, and ADAM12, BTK can be used as independent prognostic factors. The three-gene signature well stratified the LADC patients in both training (TCGA) and testing (GEO) datasets as high-risk and low-risk groups, the 3-year area under curve (AUC) of ROC curves of three GEO sets were 0.718 (GSE3141), 0.646 (GSE30219) and 0.643 (GSE50081). The GSEA analysis indicated that highly expressed ADAM12, BTK, ERG mainly correlated with the activation of pathways involving in focal adhesion, immune regulation. The immune analysis indicated that the low-risk group has more immune activities and higher expression of HLA genes than that of the high-risk group. In sum, we identified and constructed a three TME-related DEGs signature, which could be used to predict the prognosis of LADC patients.", "claims": [{"id": "claim-method", "statement": "Differentially expressed TME-related genes between LADC and normal samples were screened using Wilcoxon rank sum test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31803536", "locator": "sections[4] \"Identification of differentially expressed genes related to LADC tumor microenvironment\" paragraph 2", "quote": "Differentially expressed TME-related genes between LADC and normal samples were screened using Wilcoxon rank sum test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:The expression profile and clinical data are all from the level 3 data available in the TCGA database (https://portal.gdc.cancer.gov/repository). Search terms: “Primary Site” IS “Bronchus and lung” AND “Project Id” IS “TCGA-LUAD” AND “Workflow Type” IS “HTSeq-FPKM” AND “Data Category” IS “TranscriptomeProfiling” AND “Data Type” IS “Gene Expression Quantification.”The microarray-basedexpression data of LADC patients and associated clinical information are available at Gene Expression Omnibus: GSE3141, GSE30219, GSE50081.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31803536", "locator": "sections[19] \"Additional Information and Declarations\" paragraph 4", "quote": "The following information was supplied regarding data availability:The expression profile and clinical data are all from the level 3 data available in the TCGA database (https://portal.gdc.cancer.gov/repository). Search terms: “Primary Site” IS “Bronchus and lung” AND “Project Id” IS “TCGA-LUAD” AND “Workflow Type” IS “HTSeq-FPKM” AND “Data Category” IS “TranscriptomeProfiling” AND “Data Type” IS “Gene Expression Quantification.”The microarray-basedexpression data of LADC patients and associated clinical information are available at Gene Expression Omnibus: GSE3141, GSE30219, GSE50081."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:31803536"], "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:GSE30219"], "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:GSE30219"], "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:31803536", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.8128", "sha256": "sha256:7fa04c84bdedc82bbb8498f9ddf255f02a5f30d2a895b89d15d1f755a7f86950", "bytes": 28617, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.8128", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6886493", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE30219", "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=GSE30219", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30219", "version": null, "note": "The following information was supplied regarding data availability:The expression profile and clinical data are all from the level 3 data available in the TCGA database (https://portal.gdc.cancer.gov/repository). Search terms: “Primary Site” IS “Bronchus and lung” AND “Project Id” IS “TCGA-LUAD” AND “Workflow Type” IS “HTSeq-FPKM” AND “Data Category” IS “TranscriptomeProfiling” AND “Data Type” IS “Gene Expression Quantification.”The microarray-basedexpression data of LADC patients and associated clinical information are available at Gene Expression Omnibus: GSE3141, GSE30219, GSE50081.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:The expression profile and clinical data are all from the level 3 data available in the TCGA database (https://portal.gdc.cancer.gov/repository). 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Search terms: “Primary Site” IS “Bronchus and lung” AND “Project Id” IS “TCGA-LUAD” AND “Workflow Type” IS “HTSeq-FPKM” AND “Data Category” IS “TranscriptomeProfiling” AND “Data Type” IS “Gene Expression Quantification.”The microarray-basedexpression data of LADC patients and associated clinical information are available at Gene Expression Omnibus: GSE3141, GSE30219, GSE50081.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:The expression profile and clinical data are all from the level 3 data available in the TCGA database (https://portal.gdc.cancer.gov/repository). Search terms: “Primary Site” IS “Bronchus and lung” AND “Project Id” IS “TCGA-LUAD” AND “Workflow Type” IS “HTSeq-FPKM” AND “Data Category” IS “TranscriptomeProfiling” AND “Data Type” IS “Gene Expression Quantification.”The microarray-basedexpression data of LADC patients and associated clinical information are available at Gene Expression Omnibus: GSE3141, GSE30219, GSE50081.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM70125", "GSM70126", "GSM70127", "GSM70128", "GSM70129", "GSM70130", "GSM70131", "GSM70132", "GSM70133", "GSM70134", "GSM70135", "GSM70136", "GSM70137", "GSM70138", "GSM70139", "GSM70140", "GSM70141", "GSM70142", "GSM70143", "GSM70144", "GSM70145", "GSM70146", "GSM70147", "GSM70148", "GSM70149", "GSM70150", "GSM70151", "GSM70152", "GSM70153", "GSM70154", "GSM70155", "GSM70156", "GSM70157", "GSM70158", "GSM70159", "GSM70160", "GSM70161", "GSM70162", "GSM70163", "GSM70164", "GSM70165", "GSM70166", "GSM70167", "GSM70168", "GSM70169", "GSM70170", "GSM70171", "GSM70172", "GSM70173", "GSM70174", "GSM70175", "GSM70176", "GSM70177", "GSM70178", "GSM70179", "GSM70180", "GSM70181", "GSM70182", "GSM70183", "GSM70184", "GSM70185", "GSM70186", "GSM70187", "GSM70188", "GSM70189", "GSM70190", "GSM70191", "GSM70192", "GSM70193", "GSM70194", "GSM70195", "GSM70196", "GSM70197", "GSM70198", "GSM70199", "GSM70200", "GSM70201", "GSM70202", "GSM70203", "GSM70204", "GSM70205", "GSM70206", "GSM70207", "GSM70208", "GSM70209", "GSM70210", "GSM70211", "GSM70212", "GSM70213", "GSM70214", "GSM70215", "GSM70216", "GSM70217", "GSM70218", "GSM70219", "GSM70220", "GSM70221", "GSM70222", "GSM70223", "GSM70224", "GSM70225", "GSM70226", "GSM70227", "GSM70228", "GSM70229", "GSM70230", "GSM70231", "GSM70232", "GSM70233", "GSM70234", "GSM70235"], "sample_count": 111, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Lung Cancer Dataset", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE50081", "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=GSE50081", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50081", "version": null, "note": "The following information was supplied regarding data availability:The expression profile and clinical data are all from the level 3 data available in the TCGA database (https://portal.gdc.cancer.gov/repository). 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