A novel signature of aging-related genes associated with lymphatic metastasis for survival prediction in patients with bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37441420", "kind": "science-record", "revision": 3, "content_hash": "sha256:c321559009b296ef41660bb11b49f2e146602c37997809f930a77917573793aa", "created_at": "2026-11-01T19:02:12Z", "updated_at": "2026-11-01T22:09:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel signature of aging-related genes associated with lymphatic metastasis for survival prediction in patients with bladder cancer.", "doi": "10.3389/fonc.2023.1140891", "pmid": "37441420", "authors": ["Zhiguo Zhu", "Xiaoli Li", "Deqian Liu", "Zhonghai Li"], "journal": "Frontiers in oncology", "year": 2023, "abstract": "Background: The predominant and most prevalent form of metastatic bladder cancer (BCa) is lymphatic metastasis, which is associated with a highly dismal prognosis for patients. Aging-related genes (ARGs) are believed to contribute significantly to tumor development. However, the effect of ARGs on lymphatic metastasis of BCa is unclear. This research sought to establish a prognosis model based on ARGs associated with lymphatic metastasis in BCa.\nMethods: We downloaded BCa data from the TCGA and GEO databases and ARGs from the Aging Atlas database. The least absolute shrinkage and selection operator (LASSO) approach was applied to obtain the characteristic ARGs of risk signature in the TCGA cohort. Verification was done using the GSE13507 dataset. The R package 'ConsensusClusterPlus' was employed to identify the molecular subtypes based on the characteristic ARGs. Protein-Protein interaction network, MCODE analysis, enrichment analysis (KEGG, GO, GSEA), and immune infiltration analysis were performed to investigate underlying mechanisms. EdU, migration and invasion assays, wound healing assays, immunofluorescence staining, and quantitative polymerase chain reaction were conducted to evaluate the impact of ELN on the proliferative, migratory, and invasive capacities of BCa cells.\nResults: We identified 20 differently expressed ARGs. A four ARGs risk signature (EFEMP1, UCHL1, TP63, ELN) was constructed in the TCGA cohort. The high-risk group (category) recorded a reduced overall survival (OS) rate relative to the low-risk category (hazard ratio, 2.15; P <0.001). The risk score could predict lymphatic metastasis in TCGA cohort (AUC=0.67). The GSE13507 dataset was employed to verify the validity of this risk score. Based on the four ARGs, two distinct aging profiles (Cluster 1 and Cluster 2) were discovered utilizing the ConsensusClusterPlus, and Cluster 2 possessed a favorable OS in contrast with Cluster 1 (hazard ratio, 0.69; P =0.02). Classical tumor signaling pathways, ECM-associated signaling pathways, and immune-related signaling pathways participate in BCa progression. ELN recombinant protein affected the expression of collagen and increased migration and invasiveness in BCa cells.\nConclusion: We constructed a four-ARG risk signature and identified two aging molecular subtypes. This signature could serve as an effective survival predictor for patients with BCa.", "claims": [{"id": "claim-method", "statement": "The least absolute shrinkage and selection operator (LASSO) approach was applied to obtain the characteristic ARGs of risk signature in the TCGA cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37441420", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The least absolute shrinkage and selection operator (LASSO) approach was applied to obtain the characteristic ARGs of risk signature in the TCGA cohort."}], "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:37441420", "locator": "sections[25] \"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": "We constructed a four-ARG risk signature and identified two aging molecular subtypes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37441420", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We constructed a four-ARG risk signature and identified two aging molecular subtypes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We constructed a four-ARG risk signature and identified two aging molecular subtypes.", "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:37441420"], "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": {}, "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:37441420", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2023.1140891", "sha256": "sha256:f9e35b26a65f3c3de9912c09c9265a00d6f9eb4c05523509b057d11368e1f426", "bytes": 49025, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2023.1140891", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10335803", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13507", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13507", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13507", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . 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