Genomic and immunogenomic analysis of three prognostic signature genes in LUAD.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36650426", "kind": "science-record", "revision": 3, "content_hash": "sha256:3da818188f2906be9da23aaf1b5453a62f9fd5fbf8c6a9a2ba831be33744cd01", "created_at": "2026-11-01T19:01:12Z", "updated_at": "2026-11-01T22:08:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Genomic and immunogenomic analysis of three prognostic signature genes in LUAD.", "doi": "10.1186/s12859-023-05137-y", "pmid": "36650426", "authors": ["Hai-Ming Feng", "Ye Zhao", "Wei-Jian Yan", "Bin Li"], "journal": "BMC bioinformatics", "year": 2023, "abstract": "BACKGROUND: Searching for immunotherapy-related markers is an important research content to screen for target populations suitable for immunotherapy. Prognosis-related genes in early stage lung cancer may also affect the tumor immune microenvironment, which in turn affects immunotherapy.\nRESULTS: We analyzed the differential genes affecting lung cancer patients receiving immunotherapy through the Cancer Treatment Response gene signature DataBase (CTR-DB), and set a threshold to obtain a total of 176 differential genes between response and non-response to immunotherapy. Functional enrichment analysis found that these differential genes were mainly involved in immune regulation-related pathways. The early-stage lung adenocarcinoma (LUAD) prognostic model was constructed through the cancer genome atlas (TCGA) database, and three target genes (MMP12, NFE2, HOXC8) were screened to calculate the risk score of early-stage LUAD. The receiver operating characteristic (ROC) curve indicated that the model had good prognostic value, and the validation set (GSE50081, GSE11969 and GSE42127) from the gene expression omnibus (GEO) analysis indicated that the model had good stability, and the risk score was correlated with immune infiltrations to varying degrees. Multi-type survival analysis and immune infiltration analysis revealed that the transcriptome, methylation and the copy number variation (CNV) levels of the three genes were correlated with patient prognosis and some tumor microenvironment (TME) components. Drug sensitivity analysis found that the three genes may affect some anti-tumor drugs. The mRNA expression of immune checkpoint-related genes showed significant differences between the high and low group of the three genes, and there may be a mutual regulatory network between immune checkpoint-related genes and target genes. Tumor immune dysfunction and exclusion (TIDE) analysis found that three genes were associated with immunotherapy response and maybe the potential predictors to immunotherapy, consistent with the CTR-DB database analysis.\nCONCLUSIONS: From the perspective of data mining, this study suggests that MMP12, NFE2, and HOXC8 may be involved in tumor immune regulation and affect immunotherapy. They are expected to become markers of immunotherapy and are worthy of further experimental research.", "claims": [{"id": "claim-method", "statement": "Differential genes were screened by setting the threshold adjusted P value < = 0.05 and |logFC|> = 2, and the target genes were determined according to the AUC (Area under roc Curve) value > = 0.7.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36650426", "locator": "sections[3] \"Immunotherapy response differential genes (ImTRDG)\" paragraph 4", "quote": "Differential genes were screened by setting the threshold adjusted P value < = 0.05 and |logFC|> = 2, and the target genes were determined according to the AUC (Area under roc Curve) value > = 0.7."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36650426", "locator": "sections[35] \"Availability of data and materials\" paragraph 2", "quote": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 176 immunotherapy-response differential genes and constructed an early-stage LUAD prognostic risk score using MMP12, NFE2, and HOXC8.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36650426", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We analyzed the differential genes affecting lung cancer patients receiving immunotherapy through the Cancer Treatment Response gene signature DataBase (CTR-DB), and set a threshold to obtain a total of 176 differential genes between response and non-response to immunotherapy."}, {"asset": "source:pmid:36650426", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The early-stage lung adenocarcinoma (LUAD) prognostic model was constructed through the cancer genome atlas (TCGA) database, and three target genes (MMP12, NFE2, HOXC8) were screened to calculate the risk score of early-stage LUAD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 176 immunotherapy-response differential genes and constructed an early-stage LUAD prognostic risk score using MMP12, NFE2, and HOXC8.", "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:36650426"], "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:GSE11969"], "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": {"hazard_ratio": "lues and hazard ratios (HR) with 95% confidence in"}, "inputs": ["data:geo:GSE11969"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36650426", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12859-023-05137-y", "sha256": "sha256:61d787e1bd7e2c5aef9713264000accde6ded795f309ff3399df9d0f726e8896", "bytes": 87375, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12859-023-05137-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9843910", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE11969", "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=GSE11969", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE11969", "version": null, "note": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM302996", "GSM302997", "GSM302998", "GSM302999", "GSM303000", "GSM303001", "GSM303002", "GSM303003", "GSM303004", "GSM303005", "GSM303006", "GSM303007", "GSM303008", "GSM303009", "GSM303010", "GSM303011", "GSM303012", "GSM303013", "GSM303014", "GSM303015", "GSM303016", "GSM303017", "GSM303018", "GSM303019", "GSM303020", "GSM303021", "GSM303022", "GSM303023", "GSM303024", "GSM303025", "GSM303026", "GSM303027", "GSM303028", "GSM303029", "GSM303030", "GSM303031", "GSM303032", "GSM303033", "GSM303034", "GSM303035", "GSM303036", "GSM303037", "GSM303038", "GSM303039", "GSM303040", "GSM303041", "GSM303042", "GSM303043", "GSM303044", "GSM303045", "GSM303046", "GSM303047", "GSM303048", "GSM303049", "GSM303050", "GSM303051", "GSM303052", "GSM303053", "GSM303054", "GSM303055", "GSM303056", "GSM303057", "GSM303058", "GSM303059", "GSM303060", "GSM303061", "GSM303062", "GSM303063", "GSM303064", "GSM303065", "GSM303066", "GSM303067", "GSM303068", "GSM303069", "GSM303070", "GSM303071", "GSM303072", "GSM303073", "GSM303074", "GSM303075", "GSM303076", "GSM303077", "GSM303078", "GSM303079", "GSM303080", "GSM303081", "GSM303082", "GSM303083", "GSM303084", "GSM303085", "GSM303086", "GSM303087", "GSM303088", "GSM303089", "GSM303090", "GSM303091", "GSM303092", "GSM303093", "GSM303094", "GSM303095", "GSM303096", "GSM303097", "GSM303098", "GSM303099", "GSM303100", "GSM303101", "GSM303102", "GSM303103", "GSM303104", "GSM303105", "GSM303106", "GSM303107", "GSM303108", "GSM303109", "GSM303110", "GSM303111", "GSM303112", "GSM303113", "GSM303114", "GSM303115", "GSM303116", "GSM303117", "GSM303118", "GSM303119", "GSM303120", "GSM303121", "GSM303122", "GSM303123", "GSM303124", "GSM303125", "GSM303126", "GSM303127", "GSM303128", "GSM303129", "GSM303130", "GSM303131", "GSM303132", "GSM303133", "GSM303134", "GSM303135", "GSM303136", "GSM303137", "GSM303138", "GSM303139", "GSM303140", "GSM303141", "GSM303142", "GSM303143", "GSM303144", "GSM303145", "GSM303146", "GSM303147", "GSM303148", "GSM303149", "GSM303150", "GSM303151", "GSM303152", "GSM303153", "GSM303154", "GSM303155", "GSM303156", "GSM303157", "GSM303158"], "sample_count": 163, "group_sizes": null, "group_sizes_basis": null, "platform": "7015", "taxon": "Homo sapiens", "title": "Expression Profile-Defined Classification of Lung Adenocarcinoma", "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: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 (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3589673", "GSM3589674", "GSM3589675", "GSM3589676", "GSM3589677", "GSM3589678", "GSM3589679", "GSM3589680", "GSM3589681", "GSM3589682", "GSM3589683", "GSM3589684", "GSM3589685", "GSM3589686", "GSM3589687", "GSM3589688"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer", "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:GSE135222", "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=GSE135222", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE135222", "version": null, "note": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3995402", "GSM3995403", "GSM3995404", "GSM3995405", "GSM3995406", "GSM3995407", "GSM3995408", "GSM3995409", "GSM3995410", "GSM3995411", "GSM3995412", "GSM3995413", "GSM3995414", "GSM3995415", "GSM3995416", "GSM3995417", "GSM3995418", "GSM3995419", "GSM3995420", "GSM3995421", "GSM3995422", "GSM3995423", "GSM3995424", "GSM3995425", "GSM3995426", "GSM3995427", "GSM3995428"], "sample_count": 27, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "DNA methylation loss coupled with mitotic cell division promotes immune evasion of tumours with high mutation load [RNA-seq]", "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:GSE42127", "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=GSE42127", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE42127", "version": null, "note": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. 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The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 for this article can be found online.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets (GSE135222, GSE126044, GSE50081, GSE11969 and GSE42127) generated and analysed during the current study are available in the GEO dataset repository. https://www.ncbi.nlm.nih.gov/gds. The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. 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