To identify cancer from urine samples, Nonacus’ liquid biopsy technology will be used alongside a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the University’s Bladder Cancer Research Centre.
Bladder cancer is a disease that affects over 100,000 individuals a year in the United Kingdom. People tend to find out when they discover blood in their urine (haematuria). Firstly, a cystoscopy, which includes putting a camera into the bladder, is generally performed. Bladder cancer is detected in 12% of patients, usually after a second procedure to get a sample.
Dr Bryan, director of the Bladder Cancer Research Centre, said: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality. Unfortunately, the remaining 20% will need a further invasive procedure to confirm the diagnosis. What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”
In spite of its attractiveness, obtaining correct findings from a “liquid biopsy” needs very sensitive analytical procedures due to the tiny amounts of tumor DNA in a background of DNA from normal tissues. However, researchers at the University knew that Nonacus had pioneered commercial non-invasive prenatal tests to detect tiny amounts of fetal DNA in maternal blood samples before they began their work.
As a result of “deep sequencing” of tumour DNA, researchers were able to discover mutations found in the majority of urothelial bladder cancers (UBCs). Tumor samples from 956 newly diagnosed, treatment-nave patients were us to identify the sequencing of 23 genes. Over 96% of tumours had 451 distinct mutations, according to the study. Identifiable mutations were found in urine samples that were collected at the same time.
Cancer Research UK and the MRC Confidence in Concept grant provided funding for this project.
Tumor cells deposited into urine through the urinary tract lining can include mutant DNA, as can DNA fragments that are not attached to cancer cells. When only tiny amounts of urine are available, DNA extracted from cancer cells offers a more consistent amount of DNA for the test. Nonacus Cell3 Target’s molecular IDs and target capture technology may be used with the mutation panel to create a more sensitive test than the PCR-based technique.
The original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.
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