Development of prognostic model incorporating a ferroptosis/cuproptosis-related signature and mutational landscape analysis in muscle-invasive bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39107713", "kind": "science-record", "revision": 4, "content_hash": "sha256:4d89df2c02af01036da87f523c7009894c4898f88bb2fface45c8f5fa4693c1a", "created_at": "2026-11-01T20:29:11Z", "updated_at": "2026-11-01T22:54:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of prognostic model incorporating a ferroptosis/cuproptosis-related signature and mutational landscape analysis in muscle-invasive bladder cancer.", "doi": "10.1186/s12885-024-12741-5", "pmid": "39107713", "authors": ["Sida Hao", "Zitong Yang", "Gang Wang", "Guofeng Cai", "Yong Qin"], "journal": "BMC cancer", "year": 2024, "abstract": "BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a prevalent and aggressive malignancy. Ferroptosis and cuproptosis are recently discovered forms of programmed cell death (PCD) that have attracted much attention. However, their interactions and impacts on MIBC overall survival (OS) and treatment outcomes remain unclear.\nMETHODS: Data from the TCGA-BLCA project (as the training set), cBioPortal database, and GEO datasets (GSE13507 and GSE32894, as the test sets) were utilized to identify hub ferroptosis/cuproptosis-related genes (FRGs and CRGs) and develop a prognostic signature. Differential expression analysis (DEA) was conducted, followed by univariate and multivariate Cox's regression analyses and multiple machine learning (ML) techniques to select genetic features. The performance of the ferroptosis/cuproptosis-related signature was evaluated using Kaplan-Meier (K-M) survival analysis and receiver-operating characteristics (ROC) curves. Mutational and tumour immune microenvironment landscapes were also explored. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments confirmed the expression patterns of the hub genes, and functional assays assessed the effects of SCD knockdown on cell viability, proliferation, and migration.\nRESULTS: DEA revealed dysregulated FRGs and CRGs in the TCGA MIBC cohort. SCD, DDR2, and MT1A were identified as hub genes. A prognostic signature based on the sum of the weighted expression of these genes demonstrated strong predictive efficacy in the training and test sets. Nomogram incorporating this signature accurately predicted 1-, 3-, and 5-year survival probabilities in the TCGA cohort and GSE13507 dataset. Copy number variation (CNV) and tumour immune microenvironment analysis revealed that high risk score level groups were associated with immunosuppression and lower tumour purity. The associations of risk scores with immunotherapy and chemical drugs were also explored, indicating their potential for guiding treatment for MIBC patients. The dysregulated expression patterns of three hub genes were validated by RT-qPCR experiments.\nCONCLUSIONS: Targeting hub FRGs and CRGs could be a promising therapeutic approach for MIBC. Our prognostic model offers a new framework for MIBC subtyping and can inform personalized therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "After running voom on TCGA count matrix, differentially expressed genes (DEGs) between 17 MIBC biopsies and 17 NAT tissues were detected using the “limma” package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39107713", "locator": "sections[12] \"Identification of DEGs and co-expressed genes\" paragraph 2", "quote": "After running voom on TCGA count matrix, differentially expressed genes (DEGs) between 17 MIBC biopsies and 17 NAT tissues were detected using the “limma” package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analysed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39107713", "locator": "sections[42] \"Availability of data and materials\" paragraph 2", "quote": "No datasets were generated or analysed during the current study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified SCD, DDR2, and MT1A as hub ferroptosis/cuproptosis-related genes and developed a prognostic signature based on their weighted expression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39107713", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "SCD, DDR2, and MT1A were identified as hub genes."}, {"asset": "source:pmid:39107713", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A prognostic signature based on the sum of the weighted expression of these genes demonstrated strong predictive efficacy in the training and test sets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified SCD, DDR2, and MT1A as hub ferroptosis/cuproptosis-related genes and developed a prognostic signature based on their weighted expression.", "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:39107713"], "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:GSE13507"], "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": {"fold_change": "efined by absolute log2 fold change greater than 2 and FDR-", "fdr_threshold": "ange greater than 2 and FDR-adjusted p-value below"}, "inputs": ["data:geo:GSE13507"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39107713", "role": "manuscript", "format": 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