Posted: Friday, November 10, 2023
Disease status and treatment responses may now be monitored by observing urine tumor DNA levels, according to an article published in European Urology. “While previous methods did not provide the resolution required to reveal the mutational landscape of normal-appearing tissues, a high-resolution insight into these processes is now possible via high-throughput deep sequencing approaches,” said study author Lars Dyrskjøt, PhD, of Aarhus University Hospital, Denmark, and colleagues. This approach may eventually be used to improve the ways in which these patients are monitored and treated.
The study acquired 751 bladder biopsies and 234 urine samples from 136 patients diagnosed with non–muscle-invasive bladder cancer. All patients had also received at least five installations of bacillus Calmette-Guérin treatment. The authors ensured that biopsies and samples were taken at different points in disease progression. Biopsies and samples were then subjected to both genomic and proteomic analyses. Deep-targeted sequencing and error correction models were used to assess field cancerization in biopsies with a normal appearance.
The authors found statistical significance in the relationship between field cancerization and high tumor mutational burden, high tumor neoantigen load, and tumor-associated CD8 T-cell exhaustion. Further genomic screening of biopsies revealed that 33% of high-impact mutations were already present in biopsies that appeared to be normal, suggesting these mutations may be used to identify early disease.
Urine samples revealed that urinary tumor DNA level reflects the tumor burden within a patient. The researchers then looked at how urinary tumor DNA levels changed after treatment, finding patients with high levels had poor clinical outcomes and disease progression. The investigators pointed out that this can be used as an indicator of treatment failure. Finally, proteomic analysis demonstrated a correlation between protein levels and angiogenesis/proliferation.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.