The necroptosis signature and molecular mechanism of lung squamous cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37976123", "kind": "science-record", "revision": 4, "content_hash": "sha256:6247eb47e8d0f0f6813601083ca1ccb00a86b64cac1087bf778e47721ab5e390", "created_at": "2026-11-01T19:02:53Z", "updated_at": "2026-11-01T22:53:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The necroptosis signature and molecular mechanism of lung squamous cell carcinoma.", "doi": "10.18632/aging.205210", "pmid": "37976123", "authors": ["Guo-Qiang Song", "Hua-Man Wu", "Ke-Jie Ji", "Tian-Li He", "Yi-Meng Duan", "Jia-Wen Zhang", "Guo-Qiang Hu"], "journal": "Aging", "year": 2023, "abstract": "BACKGROUND: Given the poor prognosis of lung squamous cell carcinoma (LUSC), the aim of this study was to screen for new prognostic biomarkers.\nMETHODS: The TGCA_LUSC dataset was used as the training set, and GSE73403 was used as the validation set. The genes involved in necroptosis-related pathways were acquired from the KEGG database, and the differential genes between the LUSC and normal samples were identified using the GSEA. A necroptosis signature was constructed by survival analysis, and its correlation with patient prognosis and clinical features was evaluated. The molecular characteristics and drug response associated with the necroptosis signature were also identified. The drug candidates were then validated at the cellular level.\nRESULTS: The TCGA_LUSC dataset included 51 normal samples and 502 LUSC samples. The GSE73403 dataset included 69 samples. 159 genes involved in necroptosis pathways were acquired from the KEGG database, of which most showed significant differences between two groups in terms of genomic, transcriptional and methylation alterations. In particular, CHMP4C, IL1B, JAK1, PYGB and TNFRSF10B were significantly associated with the survival (p < 0.05) and were used to construct the necroptosis signature, which showed significant correlation with patient prognosis and clinical features in univariate and multivariate analyses (p < 0.05). Furthermore, CHMP4C, IL1B, JAK1 and PYGB were identified as potential targets of trametinib, selumetinib, SCH772984, PD 325901 and dasatinib. Finally, knockdown of these genes in LUSC cells increased chemosensitivity to those drugs.\nCONCLUSION: We identified a necroptosis signature in LUSC that can predict prognosis and identify patients who can benefit from targeted therapies.", "claims": [{"id": "claim-method", "statement": "The overall survival was analyzed by the Kaplan-Meier method in different groups, and univariate and multivariate Cox regression analyses were performed to evaluate the correlation between the necroptosis signature and clinical characteristics in the training and validation sets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37976123", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "The overall survival was analyzed by the Kaplan-Meier method in different groups, and univariate and multivariate Cox regression analyses were performed to evaluate the correlation between the necroptosis signature and clinical characteristics in the training and validation sets."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Based on the OS data of TCGA_LUSC, the patients were divided into the high- and low-risk groups using the optimal grouping threshold of 2.005388 as calculated by surv_cutpoint function.", "kind": "quantitative", "target": {"value": 0.0084, "unit": "p-value", "tolerance": null, "source": "As shown in Figure 6A, the high-risk patients had worse survival compared to the patients in the low-risk group (p = 0.0084), indicating that the necroptosis signature has prognostic significance."}, "evidence": [{"asset": "source:pmid:37976123", "locator": "sections[14] \"The necroptosis signature is associated with the prognosis and clinical characteristics of LUSC\" paragraph 2", "quote": "As shown in Figure 6A, the high-risk patients had worse survival compared to the patients in the low-risk group (p = 0.0084), indicating that the necroptosis signature has prognostic significance."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Based on the OS data of TCGA_LUSC, the patients were divided into the high- and low-risk groups using the optimal grouping threshold of 2.005388 as calculated by surv_cutpoint function.", "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:37976123"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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