ArticleInternational journal of cancer2022
Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure.
Article in International journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Trial
- Cancer Incidence and Outcomes After Kidney Transplantation in Balkan Nephropathy Patients.Journal of clinical medicine · 2026Article
- Beyond Tradition: An Integrated Toxicological, Ecological, and Public Health Perspective on Aristolochic Acids.Journal of applied toxicology : JAT · 2026Review
- Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma.Journal of cancer research and clinical oncology · 2024Article
- Article
- Transcriptomic insights into UTUC: role of inflammatory fibrosis and potential for personalized treatment.Journal of translational medicine · 2024Article
- Aristolochic acid-associated cancers: a public health risk in need of global action.Nature reviews. Cancer · 2022Review
- Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure.International journal of cancer · 2022Article
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Authors and funding
20 authors at 8 institutions in 4 countries.
Funding
Abstract
Recurrent upper tract urothelial carcinomas (UTUCs) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). Here we delineated the molecular programs underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe. We applied an integrative multiomics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative microRNA (miRNA) and messenger ribonucleic acid (mRNA) expression profiling, immunohistochemical analysis by tissue microarrays and exome and transcriptome sequencing were performed in UTUC and nontumor tissues. Urinary miRNAs of cases undergoing surgery were profiled before and after tumor resection. Ribonucleic acid (RNA) and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC-specific miRNA:mRNA networks comprising 89 miRNAs associated with 1,862 target mRNAs, involving deregulation of cell cycle, deoxyribonucleic acid (DNA) damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC-specific transcripts were confirmed at the protein level. Exome and transcriptome sequencing of UTUCs revealed AA-specific mutational signature SBS22, with 68% to 76% AA-specific, deleterious mutations propagated at the transcript level, a possible basis for neoantigen formation and immunotherapy targeting. We next identified a signature of UTUC-specific miRNAs consistently more abundant in the patients' urine prior to tumor resection, thereby defining biomarkers of tumor presence. The complex gene regulation programs of AAN-associated UTUC tumors involve regulatory miRNAs prospectively applicable to noninvasive urine-based screening of AAN patients for cancer presence and recurrence.
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