Transcriptomic Signatures in TP53 Positive and Negative Tumor Samples in NSCLC.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40798960", "kind": "science-record", "revision": 2, "content_hash": "sha256:bed45dc8a8b085374d4a0b76b022f6d5d6e1b74189ffd7630ac4c0b525235b6f", "created_at": "2026-11-01T20:30:53Z", "updated_at": "2026-11-01T21:35:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptomic Signatures in TP53 Positive and Negative Tumor Samples in NSCLC.", "doi": "10.2174/0115665232357300250805021330", "pmid": "40798960", "authors": ["Miao Xie", "Baoguang Liu", "Ziyi Chen", "Tongtong Cao", "Xiaoyan Zhang"], "journal": "Current gene therapy", "year": 2025, "abstract": "INTRODUCTION: Lung cancer, specifically non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. TP53, a crucial tumor suppressor gene, is often mutated in various cancers, including lung cancer. This study focuses on the differences in transcriptomic profiles between TP53-mutated (TP53+) and TP53-wildtype (TP53-) NSCLC tumor samples, aiming to develop a gene signature that can predict overall survival and immune response, particularly in the context of immunotherapy. It aims to identify differentially expressed genes (DEGs) associated with TP53 status in non-small cell lung cancer and develop a gene signature that can predict overall survival and immune response.\nMETHOD: Gene expression profiles from TP53-positive and TP53-negative NSCLC tumor samples were analyzed. Data were sourced from the GEO database (GSE8569, n = 69) and the TCGA database (n = 1026). Differential expression analysis was conducted to identify DEGs, which were further analyzed using LASSO regression to develop a prognostic gene signature. Quantitative PCR (qPCR) was performed to validate the expression of selected genes.\nRESULTS: A total of 535 DEGs (168 up-regulated, 367 down-regulated) were identified in TP53+ samples. Further analysis with TCGA data narrowed this down to 29 genes, from which 12 were identified as prognostic features using LASSO analysis. This 12-gene signature effectively stratified patients into low- and high-risk groups for overall survival. Differences in immune cell infiltration and immune pathway activity were significant between these groups, indicating the potential of the gene signature to predict immune response. Among the genes analyzed, BMP2, LPXN, IER3, ANLN, TNNT1, OGT, KRT8, BARX2, PRC1, and SNX30 showed statistically significant differences in qPCR results.\nDISCUSSION: The 12-gene signature demonstrates robust predictive capability for survival outcomes and immune response patterns in NSCLC patients, suggesting its potential clinical utility in precision oncology. The observed correlation between TP53 mutation status and immune microenvironment alterations provides valuable insights into the mechanistic basis of immunotherapy resistance and response.\nCONCLUSION: This study identifies a TP53-associated transcriptomic signature that is significantly associated with overall survival in lung cancer patients. The gene signature also correlates with differences in immune cell infiltration patterns between risk groups, offering potential insights into the tumor immune microenvironment. These findings may contribute to future efforts to stratify patients and guide immunotherapy decisions, pending further experimental validation.", "claims": [{"id": "claim-data-access", "statement": "The authors confirm that the data supporting the findings of this research are available within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40798960", "locator": "sections[24] \"AVAILABILITY OF DATA AND MATERIALS\" paragraph 2", "quote": "The authors confirm that the data supporting the findings of this research are available within the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This 12-gene signature effectively stratified patients into low- and high-risk groups for overall survival.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40798960", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "This 12-gene signature effectively stratified patients into low- and high-risk groups for overall survival."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This 12-gene signature effectively stratified patients into low- and high-risk groups for overall survival.", "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:40798960"], "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:GSE8569"], "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:GSE8569"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40798960", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2174/0115665232357300250805021330", "sha256": "sha256:93304d1101fa3e93235de4c210b3d207e30fe2627627b843a87c73aa9f5eed20", "bytes": 34627, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2174/0115665232357300250805021330", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC13625031", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE8569", "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=GSE8569", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE8569", "version": null, "note": "The authors confirm that the data supporting the findings of this research are available within the article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors confirm that the data supporting the findings of this research are available within the article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM212693", "GSM212694", "GSM212695", "GSM212696", "GSM212697", "GSM212698", "GSM212699", "GSM212700", "GSM212701", "GSM212702", "GSM212703", "GSM212704", "GSM212705", "GSM212706", "GSM212707", "GSM212708", "GSM212709", "GSM212710", "GSM212711", "GSM212712", "GSM212713", "GSM212714", "GSM212715", "GSM212716", "GSM212717", "GSM212718", "GSM212719", "GSM212720", "GSM212721", "GSM212722", "GSM212723", "GSM212724", "GSM212725", "GSM212726", "GSM212727", "GSM212728", "GSM212729", "GSM212730", "GSM212731", "GSM212732", "GSM212733", "GSM212734", "GSM212735", "GSM212736", "GSM212737", "GSM212738", "GSM212739", "GSM212740", "GSM212741", "GSM212742", "GSM212743", "GSM212744", "GSM212745", "GSM212746", "GSM212747", "GSM212748", "GSM212749", "GSM212750", "GSM212751", "GSM212752", "GSM212753", "GSM212754", "GSM212755", "GSM212756", "GSM212757", "GSM212758", "GSM212759", "GSM212760", "GSM212761", "GSM212762", "GSM212763", "GSM212764", "GSM212765", "GSM212766", "GSM212767"], "sample_count": 75, "group_sizes": null, "group_sizes_basis": null, "platform": "5645", "taxon": "Homo sapiens", "title": "Gene expression and lung tumors: screening for markers that discriminate tumor histology and genetic background.", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE8569 not downloaded", "asset:data:geo:GSE8569 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The R package “survival” was utilized to ascertain prognostic genes using the Cox proportional hazards method [25]."}}], "targets": [], "gaps": []}, "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE8569"], "resolved_accessions": ["GSE8569"], "statements": ["The authors confirm that the data supporting the findings of this research are available within the article."], "basis": "The paper names GSE8569 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:40798960", "data:geo:GSE8569"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE8569"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:59:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9667, "completion_tokens": 1704, "cached_tokens": 128}}, "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:40798960", "type": "paper", "label": "pmid:40798960"}, {"id": "source:pmid:40798960", "type": "manuscript", "label": "PMID 40798960 full text"}, {"id": "data:geo:GSE8569", "type": "dataset", "label": "GEO GSE8569"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40798960", "type": "paper", "label": "pmid:40798960"}, {"id": "source:pmid:40798960", "type": "manuscript", "label": "PMID 40798960 full text"}, {"id": "data:geo:GSE8569", "type": "dataset", "label": "GEO GSE8569"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40798960", "type": "extraction", "used": ["source:pmid:40798960"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE8569", "type": "accession_resolution", "used": ["data:geo:GSE8569"], "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:40798960", "parent_hash": "sha256:3a712c9defaac8d8d8c2ebadcf287eab906f9b328790de386a4075ce55c47f07", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE8569 licence not read", "asset:data:geo:GSE8569 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["prognostic gene signature. Quantitative PCR (qPCR) was performed to validate the expression of", "wed statistically significant differences in qPCR results. DISCUSSION: The 12-gene signature d"], "order_basis": "paper_text_order:1116", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The R package “survival” was utilized to ascertain prognostic genes using the Cox proportional hazards method [25]."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}