Keratin gene signature expression drives epithelial-mesenchymal transition through enhanced TGF-β signaling pathway activation and correlates with adverse prognosis in lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38322947", "kind": "science-record", "revision": 4, "content_hash": "sha256:c79fbe52d7f65b2a5e2c3af0d212b26795ed9d3a4846335225b003c72e731e21", "created_at": "2026-11-01T19:20:15Z", "updated_at": "2026-11-01T22:53:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Keratin gene signature expression drives epithelial-mesenchymal transition through enhanced TGF-β signaling pathway activation and correlates with adverse prognosis in lung adenocarcinoma.", "doi": "10.1016/j.heliyon.2024.e24549", "pmid": "38322947", "authors": ["Gang Li", "Jinbao Guo", "Yunfei Mou", "Qingsong Luo", "Xuehai Wang", "Wei Xue", "Ting Hou", "Tianyang Zeng", "Yi Yang"], "journal": "Heliyon", "year": 2024, "abstract": "Background: Lung adenocarcinoma (LUAD) stands as the foremost histological subtype of non-small-cell lung cancer, accounting for approximately 40% of all lung cancer diagnoses. However, there remains a critical unmet need to enhance the prediction of clinical outcomes and therapy responses in LUAD patients. Keratins (KRTs), serving as the structural components of the intermediate filament cytoskeleton in epithelial cells, play a crucial role in the advancement of tumor progression. This study investigated the prognostic significance of the KRT family gene and developed a KRT gene signature (KGS) for prognostic assessment and treatment guidance in LUAD.\nMethods: Transcriptome profiles and associated clinical details of LUAD patients were meticulously gathered from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The KGS score was developed based on the expression of five prognostic KRT genes (KRT7, KRT8, KRT17, KRT18, and KRT80), and the upper quartile of the KGS score was chosen as the cutoff. The Kaplan-Meier method was evaluated to compare survival outcomes between KGS-high and KGS-low groups. The underlying mechanism was further investigated by GSEA, GSVA, and other bioinformatic algorithms.\nResults: High expression of the KGS signature exhibited a robust association with poorer overall survival (OS) in the TCGA-LUAD dataset (HR: 1.81; 95% CI: 1.35-2.42, P = 0.00011). The association was further corroborated in three external GEO cohorts, including GSE31210 (HR: 3.31; 95% CI: 1.7-6.47, P = 0.00017), GSE72094 (HR: 1.95; 95% CI: 1.34-2.85, P = 0.00057) and GSE26939 (HR: 3.19; 95% CI: 1.74-5.84, P < 0.0001). Interestingly, KGS-high tumors revealed enrichments in TGF-β and WNT-β catenin signaling pathways, exhibited heightened activation of the epithelial-mesenchymal transition (EMT) pathway and proved intensified tumor stemness compared to their KGS-low counterparts. Additionally, KGS-high tumor cells exhibited increased sensitivity to several targeted agents, including gefitinib, erlotinib, lapatinib, and trametinib, in comparison to KGS-low cells.\nConclusion: This study developed a KGS score that independently predicts the prognosis in LUAD. High expression of KGS score, accompanied by upregulation of TGF-β and WNT-β catenin signaling pathways, confers more aggressive EMT and tumor progression.", "claims": [{"id": "claim-method", "statement": "The Kaplan-Meier method was employed to estimate OS utilizing the “survival” and “survminer” R packages, while the log-rank test ascertained differences in survival curves across groups stratified by varying expressions of KRT genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38322947", "locator": "sections[5] \"Survival analysis\" paragraph 2", "quote": "The Kaplan-Meier method was employed to estimate OS utilizing the “survival” and “survminer” R packages, while the log-rank test ascertained differences in survival curves across groups stratified by varying expressions of KRT genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data underlying this study are freely available from the TCGA dataset (https://portal.gdc.cancer.gov/projects/TCGA-LUAD) and the GEO dataset (http://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38322947", "locator": "sections[27] \"Data availability statement\" paragraph 2", "quote": "The data underlying this study are freely available from the TCGA dataset (https://portal.gdc.cancer.gov/projects/TCGA-LUAD) and the GEO dataset (http://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High KGS expression was associated with poorer overall survival in TCGA-LUAD and three external GEO cohorts.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "High expression of the KGS signature exhibited a robust association with poorer overall survival (OS) in the TCGA-LUAD dataset (HR: 1.81; 95% CI: 1.35–2.42, P = 0.00011). The association was further corroborated in three external GEO cohorts, including GSE31210 (HR: 3.31; 95% CI: 1.7–6.47, P = 0.00017), GSE72094 (HR: 1.95; 95% CI: 1.34–2.85, P = 0.00057) and GSE26939 (HR: 3.19; 95% CI: 1.74–5.84, P < 0.0001)."}, "evidence": [{"asset": "source:pmid:38322947", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "High expression of the KGS signature exhibited a robust association with poorer overall survival (OS) in the TCGA-LUAD dataset (HR: 1.81; 95% CI: 1.35–2.42, P = 0.00011). The association was further corroborated in three external GEO cohorts, including GSE31210 (HR: 3.31; 95% CI: 1.7–6.47, P = 0.00017), GSE72094 (HR: 1.95; 95% CI: 1.34–2.85, P = 0.00057) and GSE26939 (HR: 3.19; 95% CI: 1.74–5.84, P < 0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "High KGS expression was associated with poorer overall survival in TCGA-LUAD and three external GEO cohorts.", "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:38322947"], "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:GSE26939"], "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:GSE26939"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38322947", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2024.e24549", "sha256": 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"platform": "15048", "taxon": "Homo sapiens", "title": "KRAS mutation-associated gene expression, p53 and STK11 mutations, proliferation and immune surveillance in lung adenocarcinoma", "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:GSE26939 not downloaded", "asset:data:geo:GSE26939 licence not read", "asset:data:geo:GSE31210 not downloaded", "asset:data:geo:GSE31210 licence not read", "asset:data:geo:GSE72094 not downloaded", "asset:data:geo:GSE72094 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The 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