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pmid:39488588
Five-gene prognostic model based on autophagy-dependent cell death for predicting prognosis in lung adenocarcinoma.
Zhanshuo Zhang · Pengpeng Zhang · Jiping Xie · Yuechen Cui · Shuo Wang · Dongsheng Yue
Scientific reports · 2024 doi:10.1038/s41598-024-76186-3
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Currently, reliable indicators for predicting treatment efficacy and disease prognosis are lacking. Despite extensive validation of autophagy-dependent cell death (ADCD) in solid tumor studies and its correlation with immunotherapy effectiveness and cancer prognosis, systematic research on ADCD-related genes in LUAD is limited. We utilized AddModuleScore, ssGSEA, and WGCNA to identify genes associated with ADCD across single-cell and bulk transcriptome datasets. The TCGA dataset, comprising 598 cases, was randomly divided into training and validation sets to develop an ADCD-related LUAD prediction model. Internal validation was performed using the TCGA validation set. For external validation, datasets GSE13213 (119 LUAD samples), GSE26939 (115 LUAD samples), GSE29016 (39 LUAD samples), and GSE30219 (86 LUAD samples) were employed. We evaluated the model's accuracy and effectiveness in predicting prognostic risk. Additionally, CIBERSORT, ESTIMATE, and ssGSEA techniques were used to explore immunological characteristics, drug response, and gene expression in LUAD. Real-time RT-PCR was conducted to assess variations in mRNA expression levels of the gene XCR1 between cancerous and normal tissues in 10 lung cancer patients. We identified 249 genes associated with autophagy-dependent cell death (ADCD) at both single-cell and bulk transcriptome levels. Univariate COX regression analysis revealed that 18 genes were significantly associated with overall survival (OS). Using LASSO-Cox analysis, we developed an ADCD signature based on five genes (BIRC3, TAP1, SLAMF1, XCR1, and HLA-DMB) and created the ADCD-related risk scoring system (ADCDRS). Validation of this model demonstrated its ability to predict disease prognosis and its correlation with clinical characteristics, immune cell infiltration, and the tumor microenvironment. To enhance clinical applicability, we integrated an ADCDRS nomogram. Furthermore, we identified potential drugs targeting specific risk subgroups. We successfully identified a model based on five ADCD genes to predict disease prognosis and treatment efficacy in LUAD, as well as to assess the tumor immune microenvironment. An efficient and practical ADCDRS nomogram was designed.", "claims": [{"id": "claim-method", "statement": "Using LASSO-Cox analysis, we developed an ADCD signature based on five genes (BIRC3, TAP1, SLAMF1, XCR1, and HLA-DMB) and created the ADCD-related risk scoring system (ADCDRS).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39488588", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using LASSO-Cox analysis, we developed an ADCD signature based on five genes (BIRC3, TAP1, SLAMF1, XCR1, and HLA-DMB) and created the ADCD-related risk scoring system (ADCDRS)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE13213, GSE26939, GSE29016, and GSE30219 datasets from the Gene Expression Omnibus were acquired through the provided link [https://www.ncbi.nlm.nih.gov/geo/]. The datasets analyzed during the current study are available in The Cancer Genome Atlas repository, [https://portal.gdc.cancer.gov/projects/TCGA-LUAD]. The single-cell dataset HRA001130 from the Genome Sequence Archive (GSA) at the Beijing Institute of Genomics (BIG) Data Center was acquired through the provided link [http://bigd.big.ac.cn]. The datasets analyzed during the current study are available from the corresponding author upon reasonable request. Other data can be requested from the corresponding author for reasonable purposes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39488588", "locator": "sections[32] \"Data availability\" paragraph 2", "quote": "The GSE13213, GSE26939, GSE29016, and GSE30219 datasets from the Gene Expression Omnibus were acquired through the provided link [https://www.ncbi.nlm.nih.gov/geo/]. The datasets analyzed during the current study are available in The Cancer Genome Atlas repository, [https://portal.gdc.cancer.gov/projects/TCGA-LUAD]. 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Other data can be requested from the corresponding author for reasonable purposes."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We successfully identified a model based on five ADCD genes to predict disease prognosis and treatment efficacy in LUAD, as well as to assess the tumor immune microenvironment.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39488588", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We successfully identified a model based on five ADCD genes to predict disease prognosis and treatment efficacy in LUAD, as well as to assess the tumor immune microenvironment."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We successfully identified a model based on five ADCD genes to predict disease prognosis and treatment efficacy in LUAD, as well as to assess the tumor immune microenvironment.", "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:39488588"], "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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These cells were cultured in RPMI-1640 medium supplemented with 10% fetal", "nd two human lung adenocarcinoma cell lines (A549 and PC9), were sourced from the Cell Bank of", "e in normal cells (BEAS-2B) and tumor cells (A549, PC9). (b) Expression of XCR1 gene in 10 pai"], "order_basis": "paper_text_order:4279", "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": ["Using LASSO-Cox analysis, we developed an ADCD signature based on five genes (BIRC3, TAP1, SLAMF1, XCR1, and HLA-DMB) and created the ADCD-related risk scoring system (ADCDRS)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}