TFAP2A-activated ITGB4 promotes lung adenocarcinoma progression and inhibits CD4+/CD8+ T-cell infiltrations by targeting NF-κB signaling pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39430326", "kind": "science-record", "revision": 3, "content_hash": "sha256:67e64d0b16c84b3cee459013022e17976808fe07e9c1d7563991cbee9748c5df", "created_at": "2026-11-01T20:29:40Z", "updated_at": "2026-11-01T22:12:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "TFAP2A-activated ITGB4 promotes lung adenocarcinoma progression and inhibits CD4+/CD8+ T-cell infiltrations by targeting NF-κB signaling pathway.", "doi": "10.21037/tlcr-24-50", "pmid": "39430326", "authors": ["Cheng Pan", "Zhibo Wang", "Qi Wang", "Hongshun Wang", "Xiaheng Deng", "Liang Chen", "Zhihua Li"], "journal": "Translational lung cancer research", "year": 2024, "abstract": "Background: Immune-associated genes play vital roles in the tumorigenesis, progression and immunotherapy responses of malignant tumors. This study aimed to comprehensively evaluate the role and mechanism of novel immune-associated gene integrin β4 (ITGB4) in the progression and immune microenvironment of lung adenocarcinoma (LUAD).\nMethods: There were 770 immune-associated genes curated from NanoString PanCancer Immune Profiling Panel. Differentially expressed immune-related genes were initially screened using transcriptome data from 57 paired LUAD samples in The Cancer Genome Atlas (TCGA) and 15 paired LUAD samples in GSE31210, and were further validated in 19 paired LUAD samples from our institution. Log-rank test was adopted to identify LUAD prognosis associated genes. Among the identified differentially expressed genes, ITGB4 was ultimately chosen for further analysis. Subsequently, the functionality and mechanisms of ITGB4 were investigated in two LUAD cell lines, A549 and PC9, which exhibited relatively high expression levels of ITGB4. Following this, the impact of ITGB4 on the proliferation and metastasis of LUAD in vivo was evaluated using nude mice. Additionally, its effect on T cell infiltration was studied using immunocompetent C57BL/6J mice.\nResults: ITGB4 was found to be significantly up-regulated in LUAD and associated with an unfavorable prognosis. Functionally, ITGB4 could promote LUAD cell proliferation, migration and invasion. Consistently, in vivo experiments demonstrated that ITGB4 knockdown suppressed LUAD tumor growth and metastasis. Additionally, ITGB4 could suppress CD4+ and CD8+ T-cell infiltrations in LUAD cells. Mechanistically, ITGB4 could activate the NF-κB signaling pathway by interacting with IκBα. Furthermore, TFAP2A could directly bind to the ITGB4 promoter and transcriptionally activate ITGB4 in LUAD cells. In addition, laminin-5, a ligand of ITGB4, was found to promote LUAD progression by activating the ITGB4 signaling.\nConclusions: ITGB4 was transcriptionally activated by TFAP2A, and could promote LUAD progression and inhibit CD4+/CD8+ T-cell infiltrations by activating the NF-κB signaling pathway. ITGB4 may serve as a potential immunotherapeutic target of LUAD.", "claims": [{"id": "claim-method", "statement": "Log-rank test was adopted to evaluate the associations between immune-associated genes and LUAD prognosis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39430326", "locator": "sections[21] \"Statistical analysis\" paragraph 2", "quote": "Log-rank test was adopted to evaluate the associations between immune-associated genes and LUAD prognosis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-50/dss 10.21037/tlcr-24-50", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39430326", "locator": "sections[35] \"Data Sharing Statement\" paragraph 2", "quote": "Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-50/dss 10.21037/tlcr-24-50"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:39430326"], "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:GSE31210"], "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:GSE31210"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39430326", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tlcr-24-50", "sha256": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE31210", "GSE68465"], "resolved_accessions": ["GSE31210", "GSE68465"], "statements": ["Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-50/dss 10.21037/tlcr-24-50"], "basis": "The paper names GSE31210, GSE68465 in GSE31210 and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:39430326", "data:geo:GSE31210"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE31210"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:36:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15518, "completion_tokens": 2220, "cached_tokens": 256}}, "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:39430326", "type": "paper", "label": "pmid:39430326"}, {"id": "source:pmid:39430326", "type": "manuscript", "label": "PMID 39430326 full text"}, {"id": "data:geo:GSE31210", "type": "dataset", "label": "GEO GSE31210"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39430326", "type": "paper", "label": "pmid:39430326"}, {"id": "source:pmid:39430326", "type": "manuscript", "label": "PMID 39430326 full text"}, {"id": "data:geo:GSE31210", "type": "dataset", "label": "GEO GSE31210"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39430326", "type": "extraction", "used": ["source:pmid:39430326"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE31210", "type": "accession_resolution", "used": ["data:geo:GSE31210"], "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:39430326", "parent_hash": "sha256:6bdb7ae29d19dfc7cad72e4c85093db7ab8de5f7f4d4070a62cbed365f7d25ad", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE31210 licence not read", "asset:data:geo:GSE31210 not downloaded", "asset:data:geo:GSE68465 licence not read", "asset:data:geo:GSE68465 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["B4 were investigated in two LUAD cell lines, A549 and PC9, which exhibited relatively high exp", "Biotechnology, Shanghai, China). Cells were cultured in the RPMI-1640 medium supplemented with 1% pe", "lines H1299 (CVCL_0060), H1975 (CVCL_1511), A549 (CVCL_0023), H358 (CVCL_1559), PC9 (CVCL_B26", "water. A total of 3×106 stable cells (either A549-sh-NC or A549-sh-ITGB4) were suspended in 20"], "order_basis": "paper_text_order:1085", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["on the proliferation and metastasis of LUAD in vivo was evaluated using nude mice. Additionally,", "ation, migration and invasion. Consistently, in vivo experiments demonstrated that ITGB4 knockdow", "(PerkinElmer, Waltham, USA). After 5 weeks, mice were sacrificed, and lungs were surgically dissected. The nu", "tudy period. To ensure humane treatment, all mice were administered 2% pentobarbital sodium (40 mg/"], "order_basis": "paper_text_order:1240", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["in vivo experiments demonstrated that ITGB4 knockdown suppressed LUAD tumor growth and metastasis.", "e following assays in vivo due to its higher knockdown efficiency. Tumor growth was monitored every"], "order_basis": "paper_text_order:1629", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["mediately preserved for further experiments. Flow cytometric analysis of C57BL/6J mouse tumors Tumor samp", "rmed in fluorescence-activated cell sorting (FACS) buffer (PBS supplemented with 2% FBS). All", "PBS. Cell surface staining was performed in fluorescence-activated cell sorting (FACS) buffer (PBS supplemented with 2% FBS)", "ning was performed in fluorescence-activated cell sorting (FACS) buffer (PBS supplemented with 2% FBS)"], "order_basis": "paper_text_order:7159", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["hazard ratio; CI, confidence interval; IHC, immunohistochemistry; JSPH, Jiangsu Province Hospital; SDs, stand", "3–2.44), P<0.001, Figure S2B]. Additionally, IHC performed on 20 paired LUAD samples indicate", "ndicated that tumor tissues had higher ITGB4 IHC scores than the adjacent normal tissues (Fig", "in TCGA (E) and GSE31210 (F) datasets. (G,H) IHC analysis of ITGB4 expression in 20 paired LU"], "order_basis": "paper_text_order:10834", "id": "assay:5"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Log-rank test was adopted to evaluate the associations between immune-associated genes and LUAD prognosis."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}