In ongoing efforts to catch all forms of cancer in its early stages, researchers are making important inroads when it comes to urine and blood tests that detect the disease. Scientists in the UK have identified a promising new possibility in this area, demonstrating a first-of-a-kind test that can detect tiny DNA mutations shed by dying tumor cells in bodily fluids.
Both blood and urine tests are emerging as game-changing diagnostic tools when it comes to cancer, with a string of recent studies showing how biomarkers that represent different cancer types can be detected by analyzing these bodily fluids. This has included genetic mutations that signal bladder cancer or prostate cancers, trios of proteins that indicate pancreatic cancer and other biomarkers that reveal lung cancer via the urine.
In June, we saw evidence of this type of technology expanding to include brain cancer. Similarly, this is in the very early stages of research but the promising study showed how the genetic material microRNA produced by brain cancer cells could be detected in urine samples. Now, a team led by scientists at the University of Cambridge has made another key discovery in the same area.
The team's technology centers on what are known as cell-free DNA (cfDNA), which are tiny fragments of mutated DNA that are released into the bloodstream by cells as they die. In the case of dying tumor cells, these mutations may be the same as those seen in the primary tumor, which raises the prospect of using a blood or urine test as a screening tool for cancer.
Making things difficult with respect to brain cancer, however, is the blood-brain barrier, which prevents the fragments from entering into the blood. The cfDNA with similar mutations to the original tumor can still be found in bodily fluids, although only in low levels. The challenge has been developing a test with enough sensitivity to find them.
The Cambridge researchers have made some early, tentative steps toward overcoming this problem. Their work started with eight patients with suspected brain tumors based on MRIs, who provided samples of blood, urine and cerebrospinal fluid at the outset of the study, along with brain tumor biopsies. This enabled the team to study the DNA and know where on the strand to look for mutations in the tiny amounts of cfDNA in the urine and blood.
The test developed to seek out these mutations proved capable of detecting the tumor-specific cfDNA in 10 out of 12 blood samples and 10 out of 16 urine samples, along with seven out of eight cerebrospinal fluid samples.
Alongside this test, the team developed another that wouldn't require prior knowledge of what mutations to look for. This meant using whole genome sequencing to analyze all cfDNA arising from the brain tumor, which came from 35 glioma patients, with samples also taken from 27 subjects with non-malignant brain disorders, and 26 healthy controls.
The cfDNA found in the blood and urine samples from brain cancer patients were different in size to the healthy controls. This data was fed into a machine learning algorithm that was then able to successfully distinguish between the urine samples of the brain cancer patients and the healthy subjects, although with less accuracy than the first approach. The upside, however, is that it is cheaper, easier, and doesn't require a tissue biopsy.
It is still very early days for the technology, but the results of the study open up some exciting possibilities. The team imagines the tests finding use in screening high-risk patients who have had a brain tumor removed and are therefore vulnerable to recurrence. These patients typically undergo MRI scans and biopsies every few months to monitor for irregularities, but a blood or urine test could offer a far simpler option.
Next, the researchers plan to compare the effectiveness of the tests to MRIs, to see if they can detect recurring tumors at the same rate or perhaps even earlier on in the piece. Following that, they hope to begin adapting the technology for clinical use, which they say could eventuate sometime within the next decade.
“We believe the tests we’ve developed could in the future be able to detect a returning glioma earlier and improve patient outcomes,” says study author Richard Mair. “Talking to my patients, I know the three-month scan becomes a focal point for worry. If we could offer a regular blood or urine test, not only will you be picking up recurrence earlier, you can also be doing something positive for the patient’s mental health.”
The research was published in the journal EMBO Molecular Medicine.
Source: University of Cambridge
