Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure

Scientists from the International Agency for Research on Cancer (IARC) and partner institutions have identified a biomarker that could potentially enable non-invasive screening and monitoring of populations at increased risk of developing urothelial cancer. The results have been published in the International Journal of Cancer.

The researchers applied an integrative multi-omics analysis of upper urinary tract urothelial carcinomas arising in the context of nephropathy linked to environmental exposure to the herbal carcinogen aristolochic acid. The authors describe specific gene regulation networks operating in urothelial tumours, and their high-throughput validation at the protein level. A mutational signature of aristolochic acid was observed in the tumour DNA, and the principal aristolochic acid-specific mutation spectra and deleterious mutations were present in the mRNA of up to 50% of genes that were active in tumours. This finding suggests neoantigen formation, with potential relevance for immunotherapy.

In addition, the scientists identified a subset of urine-based microRNAs that were consistently more abundant in the patients’ urine before tumour resection. This microRNA signature may be relevant for secondary and tertiary cancer prevention, because of its potential as a non-invasive biomarker to enable screening and monitoring of the urinary tracts of patients with aristolochic acid-associated nephropathy for cancer formation as well as recurrence.

Karanović S, Ardin M, Tang Z, Tomić T, Villar S, Renard C, et al.
Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure
Int J Cancer, Published online 27 September 2021;
https://doi.org/10.1002/ijc.33827

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