Tumor microenvironment related novel signature predict lung adenocarcinoma survival.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33520448", "kind": "science-record", "revision": 7, "content_hash": "sha256:56f4ccaf39186b0af99a28bcbb1f90e328791ebbfef29fc591fb56463051a401", "created_at": "2026-11-01T15:41:23Z", "updated_at": "2026-11-01T22:03:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Tumor microenvironment related novel signature predict lung adenocarcinoma survival.", "doi": "10.7717/peerj.10628", "pmid": "33520448", "authors": ["Juan Chen", "Rui Zhou"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancers, which is the primary cause of cancer-related mortality worldwide. Growing evidence has suggested that tumor microenvironment (TME) plays a pivotal role in tumorigenesis and progression. Hence, we investigate the correlation of TME related genes with LUAD prognosis.\nMETHOD: The information of LUAD gene expression data was obtained from The Cancer Genome Atlas (TCGA). According to their immune/stromal scores calculated by the ESTIMATE algorithm, differentially expressed genes (DEGs) were identified. Then, we performed univariate Cox regression analysis on DEGs to obtain genes that are apparently bound up with LUAD survival (SurGenes). Functional annotation and protein-protein interaction (PPI) was also conducted on SurGenes. By validating the SurGenes with data sets of lung cancer from the Gene Expression Omnibus (GEO), 106 TME related SurGenes were generated. Further, intersection analysis was executed between the 106 TME related SurGenes and hub genes from PPI network, PTPRC and CD19 were obtained. Gene Set Enrichment Analysis and CIBERSORT analysis were performed on PTPRC and CD19. Based on the TCGA LUAD dataset, we conducted factor analysis and Step-wise multivariate Cox regression analysis for 106 TME related SurGenes to construct the prognostic model for LUAD survival prediction. The LUAD dataset in GEO (GSE68465) was used as the testing dataset to confirm the prognostic model. Multivariate Cox regression analysis was used between risk score from the prognostic model and clinical parameters.\nRESULT: A total of 106 TME related genes were collected in our research totally, which were markedly correlated with the overall survival (OS) of LUAD patient. Bioinformatics analysis suggest them mainly concentrated on immune response, cell adhesion, and extracellular matrix. More importantly, among 106 TME related SurGenes, PTPRC and CD19 were highly interconnected nodes among PPI network and correlated with immune activity, exhibiting significant prognostic potential. The prognostic model was a weighted linear combination of the 106 genes, by which the low-OS LUAD samples could be separated from the high-OS samples with success. This model was also able to rebustly predict the situation of survival (training set: p-value < 0.0001, area under the curve (AUC) = 0.649; testing set: p-value = 0.0009, AUC = 0.617). By combining with clinical parameters, the prognostic model was optimized. The AUC achieved 0.716 for 3 year and 0.699 for 5 year.\nCONCLUSION: A series of TME-related prognostic genes were acquired in this research, which could reflect immune disorders within TME, and PTPRC and CD19 show the potential to be an indicator for LUAD prognosis and tumor microenvironment modulation. The prognostic model constructed base on those prognostic genes presented a high predictive ability, and may have clinical implications in the overall survival prediction of LUAD.", "claims": [{"id": "claim-method", "statement": "For GSE14814 data set, the 106-gene prognostic model achived a higher C-index (C-index, 0.56; 95% CI [0.48–0.64]; p < 0.01) compared with the 9-gene biomarker (C-index, 0.50; 95% CI [0.44–0.56]; p = 0.7) (Fig. S3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33520448", "locator": "sections[23] \"Comparison with other gene expression signatures\" paragraph 2", "quote": "For GSE14814 data set, the 106-gene prognostic model achived a higher C-index (C-index, 0.56; 95% CI [0.48–0.64]; p < 0.01) compared with the 9-gene biomarker (C-index, 0.50; 95% CI [0.44–0.56]; p = 0.7) (Fig. S3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nData used for the differential expression gene analysis and prognostic model construction is available at TCGA: https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FLUAD_clinicalMatrix&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443 and https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FHiSeqV2&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443.\nData used to validate the differential expression gene and the prognostic model is available at NCBI GEO: GSE68465.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33520448", "locator": "sections[37] \"Data Availability Statement\" paragraphs 1-4", "quote": "The following information was supplied regarding data availability:\nData used for the differential expression gene analysis and prognostic model construction is available at TCGA: https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FLUAD_clinicalMatrix&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443 and https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FHiSeqV2&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443.\nData used to validate the differential expression gene and the prognostic model is available at NCBI GEO: GSE68465."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:33520448"], "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:GSE14814"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "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:GSE14814"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33520448", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.10628", "sha256": 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model construction is available at TCGA: https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FLUAD_clinicalMatrix&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443 and https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FHiSeqV2&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443.\nData used to validate the differential expression gene and the prognostic model is available at NCBI GEO: GSE68465.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nData used for the differential expression gene analysis and prognostic model construction is available at TCGA: https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FLUAD_clinicalMatrix&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443 and https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FHiSeqV2&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443.\nData used to validate the differential expression gene and the prognostic model is available at NCBI GEO: GSE68465.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1267450", "GSM1267451", "GSM1267452", "GSM1267453", "GSM1267454", "GSM1267455", "GSM1267456", "GSM1267457", "GSM1267458", "GSM1267459", "GSM1267460", "GSM1267461", "GSM1267462", "GSM1267463", "GSM1267464", "GSM1267465", "GSM1267466", "GSM1267467", "GSM1267468", "GSM1267469", "GSM1267470", "GSM1267471", "GSM1267472", "GSM1267473", "GSM1267474", "GSM1267475", "GSM1267476", "GSM1267477", "GSM1267478", "GSM1267479", "GSM1267480", "GSM1267481", "GSM1267482", "GSM1267483", "GSM1267484", "GSM1267485", "GSM1267486", "GSM1267487", "GSM1267488", "GSM1267489", "GSM1267490", "GSM1267491", "GSM1267492", "GSM370913", "GSM370914", 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differential expression gene analysis and prognostic model construction is available at TCGA: https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FLUAD_clinicalMatrix&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443 and https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FHiSeqV2&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443.\nData used to validate the differential expression gene and the prognostic model is available at NCBI GEO: GSE68465.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nData used for the differential expression gene analysis and prognostic model construction is available at TCGA: https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FLUAD_clinicalMatrix&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443 and https://xenabrowser.net/datapages/?dataset=TCGA.LUAD.sampleMap%2FHiSeqV2&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443.\nData used to validate the differential expression gene and the prognostic model is available at NCBI GEO: GSE68465.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1672281", "GSM1672282", "GSM1672283", "GSM1672284", "GSM1672285", "GSM1672286", "GSM1672287", "GSM1672288", "GSM1672289", "GSM1672290", "GSM1672291", "GSM1672292", "GSM1672293", "GSM1672294", "GSM1672295", "GSM1672296", "GSM1672297", "GSM1672298", "GSM1672299", "GSM1672300", "GSM1672301", "GSM1672302", "GSM1672303", "GSM1672304", "GSM1672305", "GSM1672306", "GSM1672307", "GSM1672308", "GSM1672309", "GSM1672310", "GSM1672311", "GSM1672312", 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