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pmid:37143472
Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps.
Yanhua Zuo · Guangyi Leng · Ping Leng
Pathology oncology research : POR · 2023 doi:10.3389/pore.2023.1610899
Paper
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Experiment
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Data
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Complete file
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Accumulating evidences have highlighted the vital role of NETs in tumor progression and diffusion. However, limited systematic studies regarding the role of NETs in LUAD have been performed. Methods: Differentially expressed NETs-related genes and their mutation landscape were identified with TCGA database. Consensus clustering analysis was performed to determine the NETs-related subtypes of LUAD. LASSO algorithm was employed to construct a prognostic signature. Moreover, GSE30219 and GSE31210 were used as independent validation. We also constructed a lncRNA-miRNA-mRNA regulatory axis with several miRNA and lncRNA databases. Results: Consensus clustering identified two NETs-related clusters in LUAD. High NETs score was correlated with a favorable overall survival, abundant immune cell infiltration, and high activity of immune response signal pathways. Six NET-related genes (G0S2, KCNJ15, S100A12, AKT2, CTSG, and HMGB1) with significant prognostic value were screened to develop a prognostic signature. LUAD patients with low-risk had a significantly favorable overall survival both in the training set and validation set. Moreover, NETs-related risk score and clinical stage could act as an independent prognostic factor for LUAD patients. Significant correlation was obtained between risk score and tumor immune microenvironment. We also identified lncRNA BCYRN1/miR-3664-5p/CTSG regulatory axis that may be involved in the progression of LUAD. Conclusion: We developed two molecular subtypes and a prognostic signature for LUAD based on NETs-related genes. This stratification could provide more evidences for estimating the prognosis and immunotherapy of LAUD patients.", "claims": [{"id": "claim-method", "statement": "After identifying the significantly prognostic NETs-related genes with univariate Cox regression analysis, we then performed LASSO cox regression analysis, which could compute the exact coefficient values of each identified association.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37143472", "locator": "sections[8] \"Development of prognostic signature based on NETs-related genes\" paragraph 2", "quote": "After identifying the significantly prognostic NETs-related genes with univariate Cox regression analysis, we then performed LASSO cox regression analysis, which could compute the exact coefficient values of each identified association."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37143472", "locator": "sections[22] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The NETs-related prognostic signature achieved AUC values of 0.671, 0.674, and 0.592 for predicting 1-, 3-, and 5-year overall survival, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37143472", "locator": "sections[17] \"Construction and validation of prognostic signature based on NET-related genes\" paragraph 2", "quote": "Further ROC curve indicated that the AUC value in 1-year, 3-year, and 5-year overall survival were 0.671, 0.674, and 0.592, respectively (Figure 6A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The NETs-related prognostic signature achieved AUC values of 0.671, 0.674, and 0.592 for predicting 1-, 3-, and 5-year overall survival, respectively.", "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:37143472"], "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. 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