Urine is one of the easiest samples to obtain. However, cell-free DNA in urine is highly fragmented, which has made it difficult to use in diagnostics - until now.
The detection of cell-free DNA (cfDNA) in urine could become a non-invasive approach to early cancer detection. Researchers at the Translational Genomics Research Institute, Arizona, analysed fragmentation patterns in cfDNA from urine and plasma in healthy individuals and cancer patients using whole-genome sequencing.1,2 They found that certain regions of the genome are protected from fragmentation in urine from healthy people, but the same regions are more fragmented in patients with cancer.
Compared to cfDNA from healthy individuals, tumour-related fragmentation patterns that ended in multiple protected regions occurred more frequently in the urine of cancer patients.
By comparing genome-wide differences in the fragmentation patterns of cfDNA in urine, the authors were able to identify urine samples from cancer patients with an AUC (area under the curve) of 0.89.
As a reminder: The AUC is the area under the ROC curve (ROC = receiver operating characteristics). For this purpose, the true positives are plotted against the false positives. The better the classification ability, the higher the AUC value. The AUC value can be interpreted as the probability that a positive value is actually recognised as such. A perfect test produces a dot in the upper left corner of the diagram, this would correspond to a hit rate of 100% (all positive objects are classified as such) and a false alarm rate of 0% (no negative object is classified as positive).3
The fragmentation profiles were remarkably consistent across individuals; the length of the DNA fragments was similar, the regions of the genome where fragmentation occurred were consistent and told researchers which cell type contributed the fragments. These characteristics were robust to pre-analytical interference, such as home collection and processing delays.
There is still a long way to go before we can detect cancer by urine examination, the authors say. Their main hope is that such non-invasive tests could help detect neoplasms at an early stage, when they are still more treatable. They examined samples from children with various malignancies, whose ailments often progress extraordinarily quickly, and from adults with pancreatic cancer, where early detection is crucial for prognosis.
These initial, promising results now need to be verified in larger patient populations and differences identified between men and women, young and old, and those with co-morbidities such as diabetes and other chronic diseases. If the study results are confirmed, the approach would be a breakthrough in detecting many types of tumours.
References:
1. Cell-free DNA in urine as potential method for cancer detection: if successful, non-invasive method could transform detection and treatment outcomes. ScienceDaily https://www.sciencedaily.com/releases/2021/02/210218094524.htm.
2. Markus, H. et al. Analysis of recurrently protected genomic regions in cell-free DNA found in urine. Science Translational Medicine 13, (2021).
3. ROC curve. http://www.statistics4u.info/fundstat_germ/ee_classifier_roc_curve.html.