US and UK Researchers Simultaneously Develop New Tests to Detect Prostate Cancer
Though still in trials, early results show tests may be more accurate than traditional clinical laboratory tests for detecting prostate cancer
Within weeks of each other, different research teams in the US and UK published findings of their respective efforts to develop a better, more accurate clinical laboratory prostate cancer test. With cancer being a leading cause of death among men—second only to heart disease according to the Centers for Disease Control and Prevention (CDC)—new diagnostics to identify prostate cancer would be a boon to precision medicine treatments for the deadly disease and could save many lives.
Researchers at the University of East Anglia (UEA) in Norwich, England, were working to improve the accuracy of the widely-used and accepted prostate-specific antigen (PSA) test. By contrast, researchers at Cedars-Sinai Cancer in Los Angeles, pursued a new liquid biopsy approach to identifying prostate cancer that uses nanotechnology.
Thus, these are two different pathways toward the goal of achieving earlier, more accurate diagnosis of prostate cancer, the holy grail of prostate cancer diagnosis.
“There is currently no single test for prostate cancer, but PSA blood tests are among the most used, alongside physical examinations, MRI scans, and biopsies,” said Dmitry Pshezhetskiy, PhD (above), Professorial Research Fellow at University of East Anglia and one of the authors of the UEA study. “However, PSA blood tests are not routinely used to screen for prostate cancer, as results can be unreliable. Only about a quarter of people who have a prostate biopsy due to an elevated PSA level are found to have prostate cancer. There has therefore been a drive to create a new blood test with greater accuracy.” With the completion of the US and UK studies, clinical laboratories may soon have a new diagnostic test for prostate cancer. (Photo copyright: University of East Anglia.)
East Anglia’s Research into a More Accurate Blood Test
Scientists at the University of East Anglia (UEA) worked with researchers from Imperial College in London, Imperial College NHS Trust, and Oxford BioDynamics to develop a new precision medicine blood test that can detect prostate cancer with greater accuracy than current methods.
The epigenetic blood test they developed, called Prostate Screening EpiSwitch (PSE), can identify cancer-specific chromosome conformations in blood samples. The test works in tandem with the standard prostate-specific antigen (PSA) blood test to diagnose prostate cancer, according to an Oxford BioDynamics press release.
The researchers evaluated their test in a pilot study involving 147 patients. They found their testing method had a 94% accuracy rate, which is higher than that of PSA testing alone. They discovered their test significantly improved the overall detection of prostate cancer in men who are at risk for the disease.
“When tested in the context of screening a population at risk, the PSE test yields a rapid and minimally invasive prostate cancer diagnosis with impressive performance,” Dmitry Pshezhetskiy, PhD, Professorial Research Fellow at UEA and one of the authors of the study told Science Daily. “This suggests a real benefit for both diagnostic and screening purposes.”
The UK scientists hope their test can eventually be used in everyday clinical practice as there is a need for a highly accurate method for prostate cancer screening that does not subject patients to unnecessary, costly, invasive procedures.
The UEA researchers published their findings in the peer-reviewed journal Cancers, titled, “Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection.”
Cedars-Sinai’s Research into Nanotechnology Cancer Testing
Researchers from Cedars-Sinai Cancer took a different approach to diagnosing prostate cancer by developing a nanotechnology-based liquid biopsy test that detects the disease even in microscopic amounts.
Their test isolates and identifies extracellular vesicles (EVs) from blood samples. EVs are microscopic non-reproducing protein and genetic material shed by all cells. Cedars-Sinai’s EV Digital Scoring Assay accurately extracts EVs from blood and analyzes them faster than similar currently available tests.
“This research will revolutionize the liquid biopsy in prostate cancer,” said oncologist Edwin Posadas, MD, Medical Director of the Urologic Oncology Program and co-director of the Experimental Therapeutics Program in Cedars-Sinai Cancer in a press release. “The test is fast, minimally invasive and cost-effective, and opens up a new suite of tools that will help us optimize treatment and quality of life for prostate cancer patients.”
The researchers tested blood samples from 40 patients with prostate cancer. They found that their EV test could distinguish between cancer localized to the prostate and cancer that has spread to other parts of the body.
Microscopic cancer deposits, called micrometastases, are not always detectable, even with advanced imaging methods. When these deposits spread outside the prostate area, focused radiation cannot prevent further progression of the disease. Thus, the ability to identify cancer by locale within the body could lead to new precision medicine treatments for the illness.
“[The EV Digital Scoring Assay] would allow many patients to avoid the potential harms of radiation that isn’t targeting their disease, and instead receive systemic therapy that could slow disease progression,” Posadas explained.
The Cedars-Sinai researchers published their findings in Nano Today, titled, “Prostate Cancer Extracellular Vesicle Digital Scoring Assay: A Rapid Noninvasive Approach for Quantification of Disease-relevant mRNAs.”
Other Clinical Laboratory Tests for Prostate Cancer Under Development
According to the American Cancer Society, the number of prostate cancer cases is increasing. One out of eight men will be diagnosed with the illness during his lifetime. Thus, developers have been working on clinical laboratory tests to accurately detect the disease and save lives for some time.
In “University of East Anglia Researchers Develop Non-Invasive Prostate Cancer Urine Test,” Dark Daily reported on a urine test also developed by scientists at the University of East Anglia that clinical laboratories can use to not only accurately diagnose prostate cancer but also determine whether it is an aggressive form of the disease.
And in “UPMC Researchers Develop Artificial Intelligence Algorithm That Detects Prostate Cancer with ‘Near Perfect Accuracy’ in Effort to Improve How Pathologists Diagnose Cancer ,” we outlined how researchers at the University of Pittsburgh Medical Center (UPMC) working with Ibex Medical Analytics in Israel had developed an artificial intelligence (AI) algorithm for digital pathology that can accurately diagnose prostate cancer. In the initial study, the algorithm—dubbed the Galen Prostate AI platform—accurately detected prostate cancer with 98% sensitivity and 97% specificity.
More research and clinical trials are needed before the new US and UK prostate cancer testing methods will be ready to be used in clinical settings. But it’s clear that ongoing research may soon produce new clinical laboratory tests and diagnostics for prostate cancer that will steer treatment options and allow for better patient outcomes.
—JP Schlingman
Related Information:
The New Prostate Cancer Blood Test with 94 Percent Accuracy
Invention: A Blood Test to Unlock Prostate Cancer Mysteries
Could a Urine Test Detect Pancreatic and Prostate Cancer? Study Shows 99% Success Rate
University of East Anglia Researchers Develop Non-Invasive Prostate Cancer Urine Test
UK Researchers Develop Clinical Laboratory Diagnostic Skin Test for Parkinson’s Inspired by Woman’s Ability to Smell the Disease before Onset of Symptoms
An assay using mass spectrometry could go to clinical trial within two years
Dark Daily has regularly observed that humans generate a variety of volatile substances—particularly in breath—which can be used for diagnostic purposes. But what if people, like certain trained animals, could smell the presence of disease before the onset of symptoms? What types of clinical laboratory testing biomarkers could be developed based on human-generated volatile organic compounds?
In “Woman Who Can Smell Parkinson’s Disease in Patients Even Before Symptoms Appear May Help Researchers Develop New Clinical Laboratory Test,” Dark Daily covered the unique story of Joy Milne, a retired nurse from Perth, Scotland, who claimed she could “smell” her husband’s Parkinson’s disease a decade before he was diagnosed with the illness.
As strange as that may sound, Milne’s olfactory abilities were confirmed by researchers at the Center for Regenerative Medicine at the University of Edinburgh and have now led to a clinical laboratory diagnostic Parkinson’s test based on body odor.
Researchers at the University of Manchester (UM) in the United Kingdom (UK) say their “breakthrough” test to diagnose Parkinson’s disease “can diagnose disease from skin swabs in three minutes,” according to a university press release.
The researchers published their findings in JACS AU, a Journal of the American Chemical Society, titled, “Paper Spray Ionization Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson’s Disease.”
Perdita Barran, PhD (right), head of the University of Manchester research team that developed the mass spectrometry Parkinson’s test, is shown above with Joy Milne (left), the retired nurse from Scotland who inspired Barran’s team to develop a new Parkinson’s biomarker and method for identifying it. “We are tremendously excited by these results which take us closer to making a diagnostic test for Parkinson’s Disease that could be used in clinic,” she said in a press release. A viable clinical laboratory test for Parkinson’s disease is greatly needed, as more than 10 million people worldwide currently live with the neurodegenerative disorder. (Photo copyright: University of Manchester.)
Using Mass Spectrometry to Analyze Sebum
The UM scientists hypothesized that the smell could be due to sebum, a light oily substance on skin that was going through a chemical change due to the Parkinson’s disease, Hull Daily Mail explained.
Increased sebum, which is produced by the sebaceous glands, is a hallmark of Parkinson’s, the researchers noted.
Their new method involves analysis of sebum using mass spectrometry, according to the JACS AU paper. The method, the researchers claim, makes it possible to diagnose Parkinson’s disease from skin swabs in three minutes.
“There are no cures for Parkinson’s, but a confirmatory diagnosis would allow [Parkinson’s patients] to get the right treatment and get the drugs that will help to alleviate their symptoms,” Perdita Barran, PhD, told the Hull Daily Mail. Barran is Chair of Mass Spectrometry in the Department of Chemistry and Director of the Michael Barber Centre for Collaborative Mass Spectrometry at UM’s Manchester Institute of Biotechnology. “What we are now doing is seeing if (hospital laboratories) can do what we’ve done in a research lab in a hospital lab,” she added.
Sebum Analyzed with Mass Spectrometry
Parkinson’s disease—the world’s fastest growing neurodegenerative disorder—needs “robust biomarkers” that could advance detection and head off onset of motor symptoms such as tremor, rigidity, and postural instability, the researchers note in their paper.
Their recent study builds on earlier 2019 findings they published in ACS Central Science about volatile compounds in sebum possibly being used as Parkinson’s biomarkers.
“Sebum is an underexplored biofluid, which is readily obtained from non-invasive skin swabs, which primarily consists of a mixture of triglycerides, cholesterol, free fatty acids, waxy esters, and squalene,” the researchers explained in their JACS AU paper.
The scientists sought, “to develop a method to analyze sebum in its native state to facilitate rapid assessment of the Parkinson’s disease status. Paper spray ionization mass spectrometry, which allows the direct analysis of compounds from paper, has previously been demonstrated to detect small molecules from unprocessed biofluids, such as blood and urine, but not to date with sebum,” they wrote.
The UM researchers used mass spectrometry to analyze sebum collected on cotton swabs from the backs of 79 people with Parkinson’s and 71 healthy individuals, BBC Scotland News reported.
Depanjan Sarkar, PhD, Research Associate, University of Manchester, further explained the technique in the UM news release:
- Sebum is taken from the swab to filter paper cut in a triangle.
- Using a solvent and voltage, sebum compounds transfer into the mass spectrometer.
“When we did this, we found more than 4,000 unique compounds of which 500 are different between people with Parkinson’s compared to the control participants,” Sarkar said.
Fatty Acids Make Assay Possible
Could fatty acids pave the way to an assay? The UM researchers believe so.
“We have identified two classes of lipids, namely [triglycerides] and diglycerides, as components of human sebum that are significantly differentially expressed in PD,” the researchers wrote in JACS AU. “Non-invasive sampling followed by PS-IM-MS [paper spray-ion mobility–mass spectrometry] analysis targeting these compounds could provide an inexpensive assay to support clinical phenotyping for the confirmatory diagnosis of Parkinson’s disease.”
A clinical trial for their test, which costs about $20, may be done within two years in Manchester area, the Daily Mail reported.
When Dark Daily reported in 2020 on Joy Milne’s unique ability to smell her husband’s Parkinson’s disease before it was formally diagnosed, we predicted a diagnostic test for Parkinson’s may be years away. And here it is, albeit with regulatory clearance needed following clinical trials.
It may in fact be possible to leverage sebum analysis to detect other diseases, the UM researchers noted.
For diagnostics developers, this story of Joy Milne and her husband Les Milne is a useful example of how, in tracking the life of a specific patient with a specific disease and close family members, researchers were able to identify a new class of biomarkers that could be used in a diagnostic assay.
It will be interesting to follow the University of Manchester researchers in their quest for a diagnostic mass spectrometry clinical laboratory test for Parkinson’s disease. According to Parkinson’s Foundation statistics, about 10 million people worldwide live with the neurodegenerative disorder. Such a new diagnostic test could be vitally important to medical laboratory care, and to patients and their families.
-Donna Marie Pocius
Related Information:
Parkinson’s Breakthrough Can Diagnose Disease from Skin Swabs in Three Minutes
Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum
Parkinson’s Test: Woman Who Smelled Disease on Husband Helps Scientists
UK Researchers Believe Somatic Mutations Play Vital Role in Aging, Longevity, and Death
Understanding why some mutations impair normal bodily functions and contribute to cancer may lead to new clinical laboratory diagnostics
New insight into the human genome may help explain the ageing process and provide clues to improving human longevity that can be useful to clinical laboratories and researchers developing cancer diagnostics. A recent study conducted at the Wellcome Sanger Institute in Cambridge, United Kingdom, suggests that the speed of DNA errors in genetic mutations may play a critical role in the lifespan and survival of a species.
To perform their research, the scientists analyzed genomes from the intestines of 16 mammalian species looking for genetic changes. Known as somatic mutations, these mutations are a natural process that occur in all cells during the life of an organism and are typically harmless. However, some somatic mutations can impair the normal function of a cell and even play a role in causing cancer.
The researchers published their findings in the journal Nature, titled, “Somatic Mutation Rates Scale with Lifespan Across Mammals.”
“Aging is a complex process, the result of multiple forms of molecular damage in our cells and tissues. Somatic mutations have been speculated to contribute to ageing since the 1950s, but studying them had remained difficult,” said Inigo Martincorena, PhD (above), Group Leader, Sanger Institute and one of the authors of the study. Greater understanding of the role DNA mutations play in cancer could lead to new clinical laboratory tools and diagnostics. (Photo copyright: Wellcome Sanger Institute.)
Lifespans versus Body Mass
The mammalian subjects examined in the study incorporated a wide range of lifespans and body masses and included humans, giraffes, tigers, mice, and the highly cancer-resistant naked mole-rat. The average number of somatic mutations at the end of a lifespan was around 3,200 for all the species studied, despite vast differences in age and body mass. It appears that species with longer lifespans can slow down their rate of genetic mutations.
The average lifespan of the humans used for the study was 83.6 years and they had a somatic mutation rate of 47 per year. Mice examined for the research endured 796 of the mutations annually and only lived for 3.7 years.
Species with similar amounts of the mutations had comparable lifespans. For example, the small, naked mole-rats analyzed experienced 93 mutations per year and lived to be 25 years of age. On the other hand, much larger giraffes encountered 99 mutations each year and had a lifespan of 24 years.
“With the recent advances in DNA sequencing technologies, we can finally investigate the roles that somatic mutations play in ageing and in multiple diseases,” said Inigo Martincorena, PhD, Group Leader, Sanger Institute, one of the authors of the study in a press release. He added, “That this diverse range of mammals end their lives with a similar number of mutations in their cells is an exciting and intriguing discovery.”
The scientists analyzed the patterns of the mutations and found that the somatic mutations accumulated linearly over time. They also discovered that the mutations were caused by similar mechanisms and the number acquired were relatively similar across all the species, despite a difference in diet and life histories. For example, a giraffe is typically 40,000 times larger than a mouse, but both species accumulate a similar number of somatic mutations during their lifetimes.
“The fact that differences in somatic mutation rate seem to be explained by differences in lifespan, rather than body size, suggests that although adjusting the mutation rate sounds like an elegant way of controlling the incidence of cancer across species, evolution has not actually chosen this path,” said Adrian Baez-Ortega, PhD, postdoctoral researcher at the Sanger Institute and one of the paper’s authors, in the press release.
“It is quite possible that every time a species evolves a larger size than its ancestors—as in giraffes, elephants, and whales—evolution might come up with a different solution to this problem. We will need to study these species in greater detail to find out,” he speculated.
Why Some Species Live Longer than Others
The researchers also found that the rate of somatic mutations decreased as the lifespan of each species increased which suggests the mutations have a likely role in ageing. It appears that humans and animals perish after accumulating a similar number of these genetic mutations which implies that the speed of the mutations is vital in ascertaining lifespan and could explain why some species live substantially longer than others.
“To find a similar pattern of genetic changes in animals as different from one another as a mouse and a tiger was surprising. But the most exciting aspect of the study has to be finding that lifespan is inversely proportional to the somatic mutation rate,” said Alex Cagan, PhD, Postdoctoral Fellow at the Sanger Institute and one of the authors of the study in the press release.
“This suggests that somatic mutations may play a role in ageing, although alternative explanations may be possible. Over the next few years, it will be fascinating to extend these studies into even more diverse species, such as insects or plants,” he noted.
Benefit of Understanding Ageing and Death
The scientists believe this study may provide insight to understanding the ageing process and the inevitability and timing of death. They surmise that ageing is likely to be caused by the aggregation of multiple types of damage to the cells and tissues suffered throughout a lifetime, including somatic mutations.
Some companies that offer genetic tests claim their products can predict longevity, despite the lack of widely accepted evidence that such tests are accurate within an acceptable range. Further research is needed to confirm that the findings of the Wellcome Sanger Institute study are relevant to understand the ageing process.
If the results are validated, though, it is probable that new direct-to-consumer (DTC) genetic tests will be developed, which could be a new revenue source for clinical laboratories.
—JP Schlingman
Related Information:
Mystery of Why Humans Die Around 80 May Finally Be Solved
UK Researchers Using Genetic Sequencing to Study Convergent Evolution Determine Molecular Data Superior to Morphology in Determining Evolutionary Relationships
Discovery calls into question accuracy of traditional methods for developing evolutionary trees of animals
Can a type of shrew be more related to an elephant than to other shrews? According to researchers at Milner Center for Evolution at the University of Bath (UB) in the United Kingdom, it’s possible, and their genetic study into convergent evolution may lead to improved use of genetic sequencing for the development of precision medicine treatments and clinical laboratory testing.
In fact, the UB study suggests traditional anatomical methods for determining the evolutionary relationships between species may not be as accurate as once thought, an article in SciTechDaily reported.
Nevertheless, the UB’s research into convergent evolution is unlocking new insights into how genes evolve over time and this new knowledge may help researchers develop genetic tests that more accurately identify different diseases and health conditions.
Additionally, studies that bring a better understanding of how beneficial genetic mutations work their way into a species’ genome might also aid researchers in developing personalized clinical laboratory testing and therapies based on manipulating a patient’s genetic sequences in ways that would be beneficial.
The UB researchers published their findings in the journal Nature Communications Biology, titled, “Molecular Phylogenies Map to Biogeography Better than Morphological Ones.”
Gene Sequencing More Accurate at Determining Evolutionary Relationships
The UB study suggests that existing evolutionary (phylogenetic) trees may need to be reconsidered. To put a finer point on the findings, a UB news release on the study states, “determining evolutionary trees of organisms by comparing anatomy rather than gene sequences is misleading.”
The UB scientists used genetic sequencing to quickly—and more cost effectively—determine evolutionary relationships as compared to traditional morphology (anatomy and structure), according to the news release.
They found genetic data that revealed surprising relationships about where the sequenced species originated, and which differed with prior conclusions that were drawn based on the species’ appearance. The findings suggest there may be need to “overturn centuries of scientific work in classifying relation of species by physical traits,” the UB scientists said.
Molecular Data Leads to New Insights into Convergent Evolution
The UB study’s use of genetic sequencing led the researchers to a greater understanding of convergent evolution, defined by “a characteristic evolving separately in two genetically unrelated groups of organisms,” according to UB.
For example, wings are a widely developed characteristic. But they are not necessarily a sign of relatedness when it comes to birds, bats, and insects.
“Now with molecular data, we can see that convergent evolution happens all the time—things we thought were closely related often turn out to be far apart on the tree of life,” Wills said, adding, “Individuals within a family don’t always look similar; it’s the same with evolutionary trees, too.”
Family Trees: Morphology Versus Molecular
In their paper, the UB researchers acknowledged the importance of phylogenies (evolutionary history of species) in areas of biology, including medicine. They aimed to study a better way to produce accurate phylogenetic trees.
“Phylogenetic relationships are inferred principally from two classes of data: morphological and molecular,” they wrote, adding, “The superiority of molecular trees has rarely been assessed empirically.”
So, they set out to compare the two approaches to building evolutionary trees:
- Traditional morphology analysis, and
- Phylogenetic trees developed using molecular data.
Using 48 pairs of morphological and molecular trees, they mapped data geographically.
“We show that, on average, molecular trees provide a better fit to biogeographic data than their morphological counterparts, and that biogeographic congruence increases over research time,” the researchers wrote.
Biogeography a Better Gauge of Relatedness than Anatomy
The study also found animals on molecular trees lived geographically closer as compared to groups on morphological trees.
For example, molecular studies put aardvarks, elephants, golden moles, swimming manatees, and elephant shews in an Afrotheria group, named for Africa, which is where they came from. Therefore, the biogeography matches, however the appearances of these mammals clearly do not, the UB scientists point out.
“What’s most exciting is that we find strong statistical proof of molecular trees fitting better not just in groups like Afrotheria, but across the tree of life in birds, reptiles, insects, and plants,” said Jack Oyston PhD, UB Department of Biology and Biochemistry Research Associate and first author of the study, in the news release.
The researchers believe their findings support the accuracy of genetic-themed trees.
“It being such a widespread pattern makes it much more potentially useful as a general test of different evolutionary trees. But it also shows just how pervasive convergent evolution has been when it comes to misleading us,” Oyston added.
Advantages of Molecular Data
In their Nature Communications Biology paper, the UB scientists wrote that molecular data offer up these advantages over morphology:
- Widely available in vast quantity.
- Opportunity exists to “search, repurpose, and reanalyze sequenced data alongside novel sequences.”
- Less subjectivity in researchers’ analysis.
- Well-developed data at the ready and “still in their infancy.”
The University of Bath’s study of convergent evolution, phylogenetic trees, and comparison of molecular data versus morphology, has implications for medical laboratories. Should their research lead to new insights into how genes evolve over time, diagnostics professionals may have new information to identity diseases and work with others to precisely treat patients.
—Donna Marie Pocius
Related Information:
Study Suggests That Most of Our Evolutionary Trees Could Be Wrong
Molecular Phylogenies Map to Biogeography Better than Morphological Ones
Convergent Evolution Has Been Fooling Us: Most of Our Evolutionary Trees Could Be Wrong
