Deciphering molecular overlaps between COPD and NSCLC subtypes (LUAD and LUSC): An integrative bioinformatics study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40826767", "kind": "science-record", "revision": 3, "content_hash": "sha256:343fd8bb2bfd65bc81cc02a756fb1eb7599cd86faf48d56025f01af2e624413e", "created_at": "2026-11-01T20:30:55Z", "updated_at": "2026-11-01T22:14:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deciphering molecular overlaps between COPD and NSCLC subtypes (LUAD and LUSC): An integrative bioinformatics study.", "doi": "10.1097/MD.0000000000043906", "pmid": "40826767", "authors": ["Sevinç Akçay"], "journal": "Medicine", "year": 2025, "abstract": "Chronic obstructive pulmonary disease (COPD) and non-small-cell lung cancer (NSCLC) are major global health problems. Despite clinical differences, emerging evidence suggests common molecular underpinnings, particularly between COPD and the 2 primary NSCLC subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In this integrative bioinformatics case-control study, we analyzed gene expression datasets (GSE76925, GSE18842, and GSE10072) obtained from the Gene Expression Omnibus (GEO) database, each comprising case-control samples. Differentially expressed genes (DEGs) were identified in COPD, LUAD, and LUSC patients. We performed analyses of protein-protein interaction (PPI) networks, investigated regulatory networks involving transcription factors (TFs) and microRNAs (miRNAs), and conducted pathway enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. Drug-gene interactions were assessed to explore therapeutic opportunities. We identified 15 shared DEGs between COPD, LUAD, and LUSC, with distinct gene expression patterns between COPD-LUAD and COPD-LUSC. Notably, LUAD exhibited stronger molecular similarities with COPD than with LUSC. PPI analysis revealed COL10A1, POSTN, SPP1, MMP11, and GREM1 as key hub genes in extracellular matrix (ECM) remodeling and tumor progression. Functional enrichment highlighted ECM organization, apoptosis regulation, and transcriptional control as crucial processes in COPD-associated NSCLC. COPD-LUAD was enriched in cancer-related pathways, while COPD-LUSCs showed stronger immune and lipid metabolism involvement. Regulatory network analysis identified SP1 as a key transcriptional regulator, particularly in COPD-LUAD cells. miRNA-DEG interactions highlighted \"hsa-miR-335-5p,\" \"hsa-miR-192-5p,\" and \"hsa-miR-215-5p\" as the central regulators of COPD and NSCLC. Drug-gene interaction analysis identified Marimastat, Bosentan, and Minocycline as potential therapeutic agents that target key molecular pathways shared across COPD, LUAD and LUSC. Finally, survival analysis revealed that SPP1 (in LUAD), POSTN, and GREM1 (in LUSC) were significantly associated with better overall survival, suggesting their dual utility as both biomarkers and prognostic indicators. Our research highlights the unique regulatory distinctions between LUAD and LUSC while offering fresh insights into the molecular pathways that COPD and NSCLC share. This study represents the initial effort to map TF-miRNA-DEG-drug networks across COPD and both the LUAD and LUSC subtypes. These results suggest potential biomarkers for early diagnosis and highlight opportunities for drug repurposing to mitigate COPD-associated lung cancer risk.", "claims": [{"id": "claim-method", "statement": "DEGs were classified into 3 groups: Group 1: COPD, LUSC, and LUAD; Group 2: COPD and LUSC; and Group 3: COPD and LUAD by the GEO2R statistical tool.[16] P < .05, log2FC > 1 (upregulated DEGs), or P < .05, and log2FC < 1 (downregulated DEGs) were the criteria used to identify DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40826767", "locator": "sections[4] \"2.2. Identification of common DEGs\" paragraph 2", "quote": "DEGs were classified into 3 groups: Group 1: COPD, LUSC, and LUAD; Group 2: COPD and LUSC; and Group 3: COPD and LUAD by the GEO2R statistical tool.[16] P < .05, log2FC > 1 (upregulated DEGs), or P < .05, and log2FC < 1 (downregulated DEGs) were the criteria used to identify DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40826767", "locator": "sections[22] \"(untitled)\" paragraph 1", "quote": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 15 differentially expressed genes shared among COPD, LUSC, and LUAD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40826767", "locator": "sections[11] \"3.1. Identification of common DEGs\" paragraph 2", "quote": "Fifteen common DEGs were identified in COPD, LUSC, and LUAD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 15 differentially expressed genes shared among COPD, LUSC, and LUAD.", "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:40826767"], "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:GSE10072"], "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:GSE10072"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40826767", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000043906", "sha256": "sha256:082a2610de8f061196d03eff507b0bdce7fb065b082e2b72c327178a3cba3676", "bytes": 45579, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1097/MD.0000000000043906", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12366952", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE10072", "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=GSE10072", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE10072", "version": null, "note": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM254625", "GSM254626", "GSM254627", "GSM254628", "GSM254629", "GSM254630", "GSM254631", "GSM254632", "GSM254633", "GSM254634", "GSM254635", "GSM254636", "GSM254637", "GSM254638", "GSM254639", "GSM254640", "GSM254641", "GSM254642", "GSM254643", "GSM254644", "GSM254645", "GSM254646", "GSM254647", "GSM254648", "GSM254649", "GSM254650", "GSM254651", "GSM254652", "GSM254653", "GSM254654", "GSM254655", "GSM254656", "GSM254657", "GSM254658", "GSM254659", "GSM254660", "GSM254661", "GSM254662", "GSM254663", "GSM254664", "GSM254665", "GSM254666", "GSM254667", "GSM254668", "GSM254669", "GSM254670", "GSM254671", "GSM254672", "GSM254673", "GSM254674", "GSM254675", "GSM254676", "GSM254677", "GSM254678", "GSM254679", "GSM254680", "GSM254681", "GSM254682", "GSM254683", "GSM254684", "GSM254685", "GSM254686", "GSM254687", "GSM254688", "GSM254689", "GSM254690", "GSM254691", "GSM254692", "GSM254693", "GSM254694", "GSM254695", "GSM254696", "GSM254697", "GSM254698", "GSM254699", "GSM254700", "GSM254701", "GSM254702", "GSM254703", "GSM254704", "GSM254705", "GSM254706", "GSM254707", "GSM254708", "GSM254709", "GSM254710", "GSM254711", "GSM254712", "GSM254713", "GSM254714", "GSM254715", "GSM254716", "GSM254717", "GSM254718", "GSM254719", "GSM254720", "GSM254721", "GSM254722", "GSM254723", "GSM254724", "GSM254725", "GSM254726", "GSM254727", "GSM254728", "GSM254729", "GSM254730", "GSM254731"], "sample_count": 107, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival", "resolution_checked_at": "2026-11-01T15:30:21Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE18842", "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=GSE18842", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE18842", "version": null, "note": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM466947", "GSM466948", "GSM466949", "GSM466950", "GSM466951", "GSM466952", "GSM466953", "GSM466954", "GSM466955", "GSM466956", "GSM466957", "GSM466958", "GSM466959", "GSM466960", "GSM466961", "GSM466962", "GSM466963", "GSM466964", "GSM466965", "GSM466966", "GSM466967", "GSM466968", "GSM466969", "GSM466970", "GSM466971", "GSM466972", "GSM466973", "GSM466974", "GSM466975", "GSM466976", "GSM466977", "GSM466978", "GSM466979", "GSM466980", "GSM466981", "GSM466982", "GSM466983", "GSM466984", "GSM466985", "GSM466986", "GSM466987", "GSM466988", "GSM466989", "GSM466990", "GSM466991", "GSM466992", "GSM466993", "GSM466994", "GSM466995", "GSM466996", "GSM466997", "GSM466998", "GSM466999", "GSM467000", "GSM467001", "GSM467002", "GSM467003", "GSM467004", "GSM467005", "GSM467006", "GSM467007", "GSM467008", "GSM467009", "GSM467010", "GSM467011", "GSM467012", "GSM467013", "GSM467014", "GSM467015", "GSM467016", "GSM467017", "GSM467018", "GSM467019", "GSM467020", "GSM467021", "GSM467022", "GSM467023", "GSM467024", "GSM467025", "GSM467026", "GSM467027", "GSM467028", "GSM467029", "GSM467030", "GSM467031", "GSM467032", "GSM467033", "GSM467034", "GSM467035", "GSM467036", "GSM467037"], "sample_count": 91, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression analysis of human lung cancer and control samples", "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:GSE76925", "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=GSE76925", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76925", "version": null, "note": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2040792", "GSM2040793", "GSM2040794", "GSM2040795", "GSM2040796", "GSM2040797", "GSM2040798", "GSM2040799", "GSM2040800", "GSM2040801", "GSM2040802", "GSM2040803", "GSM2040804", "GSM2040805", "GSM2040806", "GSM2040807", "GSM2040808", "GSM2040809", "GSM2040810", "GSM2040811", "GSM2040812", "GSM2040813", "GSM2040814", "GSM2040815", "GSM2040816", "GSM2040817", "GSM2040818", "GSM2040819", "GSM2040820", "GSM2040821", "GSM2040822", "GSM2040823", "GSM2040824", "GSM2040825", "GSM2040826", "GSM2040827", "GSM2040828", "GSM2040829", "GSM2040830", "GSM2040831", "GSM2040832", "GSM2040833", "GSM2040834", "GSM2040835", "GSM2040836", "GSM2040837", "GSM2040838", "GSM2040839", "GSM2040840", "GSM2040841", "GSM2040842", "GSM2040843", "GSM2040844", "GSM2040845", "GSM2040846", "GSM2040847", "GSM2040848", "GSM2040849", "GSM2040850", "GSM2040851", "GSM2040852", "GSM2040853", "GSM2040854", "GSM2040855", "GSM2040856", "GSM2040857", "GSM2040858", "GSM2040859", "GSM2040860", "GSM2040861", "GSM2040862", "GSM2040863", "GSM2040864", "GSM2040865", "GSM2040866", "GSM2040867", "GSM2040868", "GSM2040869", "GSM2040870", "GSM2040871", "GSM2040872", "GSM2040873", "GSM2040874", "GSM2040875", "GSM2040876", "GSM2040877", "GSM2040878", "GSM2040879", "GSM2040880", "GSM2040881", "GSM2040882", "GSM2040883", "GSM2040884", "GSM2040885", "GSM2040886", "GSM2040887", "GSM2040888", "GSM2040889", "GSM2040890", "GSM2040891", "GSM2040892", "GSM2040893", "GSM2040894", "GSM2040895", "GSM2040896", "GSM2040897", "GSM2040898", "GSM2040899", "GSM2040900", "GSM2040901", "GSM2040902", "GSM2040903", "GSM2040904", "GSM2040905", "GSM2040906", "GSM2040907", "GSM2040908", "GSM2040909", "GSM2040910", "GSM2040911", "GSM2040912", "GSM2040913", "GSM2040914", "GSM2040915", "GSM2040916", "GSM2040917", "GSM2040918", "GSM2040919", "GSM2040920", "GSM2040921", "GSM2040922", "GSM2040923", "GSM2040924", "GSM2040925", "GSM2040926", "GSM2040927", "GSM2040928", "GSM2040929", "GSM2040930", "GSM2040931", "GSM2040932", "GSM2040933", "GSM2040934", "GSM2040935", "GSM2040936", "GSM2040937", "GSM2040938", "GSM2040939", "GSM2040940", "GSM2040941", "GSM2040942"], "sample_count": 151, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Functional interactors of genomewide association study genes are differentially expressed in severe chronic obstructive pulmonary disease lung tissue", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE10072 not downloaded", "asset:data:geo:GSE10072 licence not read", "asset:data:geo:GSE18842 not downloaded", "asset:data:geo:GSE18842 licence not read", "asset:data:geo:GSE76925 not downloaded", "asset:data:geo:GSE76925 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "GEO2R statistical tool", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs were classified into 3 groups: Group 1: COPD, LUSC, and LUAD; Group 2: COPD and LUSC; and Group 3: COPD and LUAD by the GEO2R statistical tool.[16] P < .05, log2FC > 1 (upregulated DEGs), or P < .05, and log2FC < 1 (downregulated DEGs) were the criteria used to identify DEGs."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE76925", "GSE18842", "GSE10072"], "resolved_accessions": ["GSE76925", "GSE18842", "GSE10072"], "statements": ["The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE76925, GSE18842, GSE10072 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:40826767", "data:geo:GSE10072"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE10072"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:59:50Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13085, "completion_tokens": 1504, "cached_tokens": 264}}, "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:40826767", "type": "paper", "label": "pmid:40826767"}, {"id": "source:pmid:40826767", "type": "manuscript", "label": "PMID 40826767 full text"}, {"id": "data:geo:GSE10072", "type": "dataset", "label": "GEO GSE10072"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40826767", "type": "paper", "label": "pmid:40826767"}, {"id": "source:pmid:40826767", "type": "manuscript", "label": "PMID 40826767 full text"}, {"id": "data:geo:GSE10072", "type": "dataset", "label": "GEO GSE10072"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40826767", "type": "extraction", "used": ["source:pmid:40826767"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE10072", "type": "accession_resolution", "used": ["data:geo:GSE10072"], "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:40826767", "parent_hash": "sha256:9d6d4a376b14f62dd7a7b197af3bc6bfa7ab410e183098633d7819ce312cfe2c", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE10072 licence not read", "asset:data:geo:GSE10072 not downloaded", "asset:data:geo:GSE18842 licence not read", "asset:data:geo:GSE18842 not downloaded", "asset:data:geo:GSE76925 licence not read", "asset:data:geo:GSE76925 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["nal enrichment highlighted ECM organization, apoptosis regulation, and transcriptional control as c"], "order_basis": "paper_text_order:1493", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}