ArticleMolecular medicine (Cambridge, Mass.)2025
Genomic subtypes of non-muscle-invasive bladder cancer: guiding immunotherapy decision-making for patients exposed to aristolochic acid.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Nutraceuticals in Uro-Oncology: A Structured Expert Review and Precision-Oriented Framework.Nutrients · 2026Review
- Prognostic Value of the Inflammatory Burden Index (IBI) in Metastatic Urothelial Carcinoma Prior to First-Line Therapy.Medicina (Kaunas, Lithuania) · 2026Article
- Review
- Bladder Cancer Biomarkers: Recent Advances in Early Detection, Treatment Prediction, and Prognosis.Oncology research · 2026Review
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Authors and funding
10 authors.
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Abstract
backgroundThe limited genomic data on non-muscle-invasive bladder cancer (NMIBC) hampers our understanding of its carcinogenesis and development. Specifically, Aristolochic acid (AA), a potent human carcinogenic compound from aristolochia plants and commonly found in Chinese herbal medicine, has been extensively documented as being closely associated with the onset and progression of bladder cancer. However, the field of AA-induced NMIBC remains largely unexplored in terms of its genomic and molecular characteristics, as well as clinical therapeutic strategies.
methodsTo bridge this knowledge gap, we conducted a comprehensive study using a cohort of 81 NMIBC samples. We performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) to obtain detailed genomic and transcriptomic data. We subjected these datasets to genomic analysis and subtype analysis to gain valuable insights into NMIBC.
resultsBy temporally dissecting mutations in NMIBC specimens, we identified a comprehensive mutational landscape of NMIBC and the associations of these mutations with recurrence-free survival. Additionally, we discerned four genomic subtypes of NMIBC: AA-like, FGFR3/HRAS, FGFR3 & chr9Del, and genome instability (GI). The AA-like subtype presented a high frequency of gene mutations along with a pronounced AA mutagenesis signature of SBS22 (Fisher test: P-value 3.5e-4, OR 25.25) even after temporal dissection. The FGFR3/HRAS subtype exhibited FGFR3 or HRAS mutations with few copy number alterations (CNAs). The FGFR3 & chr9Del subtype was characterized by the co-occurrence of chr9p and chr9q deletions as well as FGFR3 mutations, while the GI subtype showed a high frequency of CNAs. Notably, the AA-like and GI subtypes demonstrated better outcomes after immunotherapy, whereas the FGFR3/HRAS subtype showed poorer outcomes.
conclusionsOur findings provide novel perspectives on the genomics of NMIBC, unveiling four prominent genomic subtypes, each showing different outcomes following immunotherapy.
trial registrationNo. 2019PHB268-01 (retrospectively registered on February 14, 2020).
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