Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35433683", "kind": "science-record", "revision": 5, "content_hash": "sha256:e5fa951e637b36f291395ae5df76757ec7c0369c9e4c9f031ea7fc363c17515e", "created_at": "2026-11-01T18:14:16Z", "updated_at": "2026-11-01T22:48:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients.", "doi": "10.3389/fcell.2022.725024", "pmid": "35433683", "authors": ["Hongbing Gu", "Chaozhao Liang"], "journal": "Frontiers in cell and developmental biology", "year": 2022, "abstract": "The clinical outcome of heterogeneous bladder cancer (BCa) is impacted by varying molecular characteristics and clinical features, and new molecular classification is necessary to recognize patients with dichotomized prognosis. We enrolled a total of 568 BCa patients from the TCGA-BLCA and GSE13507 cohorts. A total of 107 candidate genes, which were mostly involved in the extracellular matrix-associated pathway, were first selected through the consensus value of the area under the receiver operating characteristic curve (AUC). Furthermore, absolute shrinkage and selection operation regression analysis was implemented to reveal the 15 genes and establish the prognostic signature. The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76-3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76-3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208-34.731). Multivariate Cox analysis involving the signature and clinical features indicated that the signature is an independent factor for the prediction of BCa prognosis. We also explored potential targeted therapy for BCa patients with high- or low-risk scores and found that patients with high risk were more suitable for chemotherapy with gemcitabine, doxorubicin, cisplatin, paclitaxel, and vinblastine (all p < 0.05), but anti-PD-L1 therapy was useless. We knocked down HEYL with siRNAs in T24 and 5,637 cells, and observed the decreased protein level of HEYL, and inhibited cell viability and cell invasion. In summary, we proposed and validated a 15-top-prognostic gene-based signature to indicate the dichotomized prognosis and response to targeted therapy.", "claims": [{"id": "claim-method", "statement": "The receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated by the “pROC” package to assess the prognostic ability of all included genes and screen the genes included in the analysis with optimal cutoff values (TCGA-BLCA: 0.60; GSE13507: 0.65). Furthermore, to construct an accurate prognostic model, the least absolute shrinkage and selector operation (LASSO) regression analysis was implemented for screening candidate genes by using the “glmnet” package. The minimum lambda value was defined as a cutoff point to minimize the mean cross-validated error. 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The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76–3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76–3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208–34.731).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76–3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76–3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208–34.731)."}, "evidence": [{"asset": "source:pmid:35433683", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76–3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76–3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208–34.731)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76–3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76–3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208–34.731).", "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:35433683"], "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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Cell Culture, Proliferation, Invasion, and Western Blotting We cultured the T24 and 5,637 BCa cell lines", "nder a light microscope (Nikon Corporation). 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