Study is expected to result in new clinical laboratory test biomarkers based on proteins shown to be associated with specific diseases
In January, the UK Biobank announced the launch of the “world’s most comprehensive study” of the human proteome. The study focuses on proteins circulating throughout the human body. Researchers involved in this endeavor hope the project will transform disease detection and lead to clinical laboratory blood tests that help diagnosticians identify illnesses earlier than with conventional diagnostics.
Building on the results of a 2023 pilot project that studied “the effects of common genetic variation on proteins circulating in the blood and how these associations can contribute to disease,” according to a UK Biobank news release, the 2025 UK Biobank Pharma Proteomics Project (UKB-PPP) plans to analyze up to 5,400 proteins in 600,000 samples to explore how an individual’s protein levels changes over time and how those changes may influence the existence of diseases in mid-to-late life.
The specimens being analyzed include 500,000 samples extracted from UK Biobank participants and an additional 100,000 set of second samples taken from volunteers up to 15 years later.
“The data collected in the study will allow scientists around the world to conduct health-related research, exploring how lifestyle, environment, and genetics lead through proteins to some people developing particular diseases, while others do not,” Sir Rory Collins, FMedSci FRS, professor of medicine and epidemiology at University of Oxford and principal investigator and chief executive of the UK Biobank, told The Independent.
“That will allow us to identify who it is, who’s likely to develop disease well before they do, and we can then look at ways in which to prevent those conditions before they develop,” he added.
“It really might be possible to develop simple blood tests that can detect disease much earlier than currently exists,” said Naomi Allen, MSc, DPhil (above), chief scientist for UK Biobank and professor of epidemiology at Oxford Population Health, University of Oxford, in an interview with The Independent. “So, it adds a crucial piece in the jigsaw puzzle for scientists to figure out how disease develops and gives us firm clues on what we can do to prevent and treat it.” Clinical laboratories may soon have new test biomarkers that help identify proteins associated with specific diseases. (Photo copyright: UK Biobank.)
Developing New Protein-based Biomarkers
A proteome is the entire set of proteins expressed by an organism, cell, or tissue and the study of the proteome is known as proteomics. The proteome is an expression of an organism’s genome, but it can change over time between cell types and growth conditions.
The human genome contains approximately 20,000 genes and human cells have between 80,000 and 400,000 proteins with specific cells having their own proteomes. Proteomics can help ascertain how proteins function and interact with each other and assist in the identification of biomarkers for new drug discoveries and development.
“This is hugely valuable, because it will enable researchers to see how changes in protein levels within individuals over mid- to late-life influence the development of a whole range of different diseases,” said Naomi Allen, MSc, DPhil, chief scientist for UK Biobank and professor of epidemiology at the Oxford Population Health, University of Oxford, in The Independent. “It will accelerate research into the causes of disease and the development of new treatments that target specific proteins associated with those diseases.
“The pilot data is already showing that specific proteins are elevated in those who go on to develop many different types of cancers up to seven years before a clinical diagnosis is made. And for dementia, up to 10 years before clinical diagnosis is made,” she added.
According to the project’s website, the UK Biobank’s proteomics dataset will allow researchers to:
Examine proteomic and genetic data from half a million people to provide a more detailed picture of the biological processes involved in disease progression.
Examine how and why protein levels change over time to understand age-related changes in healthy individuals.
Utilize proteomic data together with imaging data to understand disease mechanisms.
“Data from the pilot study has shown that specific proteins are substantially elevated in individuals with autoimmune conditions like multiple sclerosis and Crohn’s disease and so on,” Allen noted. “So, you can see how a simple blood test could be used to complement existing diagnostic measures in order to diagnose these types of diseases more accurately and perhaps more quickly.”
An Invaluable Resource of Knowledge
The initial UK Biobank started in 2006 and, to date, has collected biological and medical data from more than half a million individuals. The subjects of the UKB-PPP study are between the ages of 40 and 69 and reside in the UK. The database is globally accessible to approved researchers and scientists engaging in research into various diseases.
The full dataset of the latest research is expected to be added to the UK Biobank Research Analysis Platform by the year 2027. The newest study is backed by a consortium of 14 pharmaceutical firms.
Allen also noted that evidence from the research has emphasized how some drugs may be useful in treating a variety of conditions.
“Some proteins that are known to be important for immunity are related to developing a range of psychiatric conditions like schizophrenia, depression, bipolar disorder and so on,” she told The Independent. “And given there are drugs already available that specifically target some of these proteins that are used for other conditions, it presents a real opportunity for repurposing those existing drugs for these neuropsychiatric conditions.”
This type of comprehensive study of the human proteome may have a great impact on patient diagnosis and treatment once the study is completed and the results are disclosed.
“The data will be invaluable. The value of the data is infinite,” Collins told The Independence.
Since it is clinical laboratories that will be engaged in testing for proteins that have become associated with specific diseases, this new UK Biobank study has the potential to expand knowledge about useful protein markers for both diagnosis and therapeutic solutions (prescription drugs).
Study findings could lead to new clinical laboratory screening tests that determine risk for cancer
New disease biomarkers generally lead to new clinical laboratory tests. Such may be the case in an investigational study conducted at the University of Oxford in the United Kingdom (UK). Researchers in the university’s Cancer Epidemiology Unit (CEU) have discovered certain proteins that appear to indicate the presence of cancer years before the disease is diagnosed.
The Oxford scientists “investigated associations between 1,463 plasma proteins and 19 cancers, using observational and genetic approaches in participants of the UK Biobank. They found 618 protein-cancer associations and 317 cancer biomarkers, which included 107 cases detected over seven years before the diagnosis of cancer,” News Medical reported.
To conduct their study, the scientists turned to “new multiplex proteomics techniques” that “allow for simultaneous assessment of proteins at a high-scale, especially those that remain unexplored in the cancer risk context,” News Medical added.
Many of these proteins were in “blood samples of people who developed cancer more than seven years before they received a diagnosis,” an Oxford Population Health news release notes.
“To be able to prevent cancer, we need to understand the factors driving the earliest stages of its development. These studies are important because they provide many new clues about the causes and biology of multiple cancers, including insights into what’s happening years before a cancer is diagnosed,” said Ruth Travis, BA, MSc, DPhil, senior molecular epidemiologist at Oxford Population Health and senior study author, in the news release.
“We now have technology that can look at thousands of proteins across thousands of cancer cases, identifying which proteins have a role in the development of specific cancers and which may have effects that are common to multiple cancer types,” said Ruth Travis, BA, MSc, DPhil (above), senior molecular epidemiologist, Oxford Population Health, in a news release. The study findings could lead to new clinical laboratory screening tests for cancer. (Photo copyright: University of Oxford.)
Proteomics to Address Multiple Cancers Analysis
In their published paper, the Oxford scientists acknowledged other research that identified links between blood proteins and risk for various cancers, including breast, colorectal, and prostate cancers. They saw an opportunity to use multiplex proteomics methods for the simultaneous measurement of proteins “many of which have not previously been assessed for their associations with risk across multiple cancer sites,” the researchers noted.
The researchers described “an integrated multi-omics approach” and the use of the Olink Proximity Extension Assay (PEA) to quantify 1,463 proteins in blood samples from 44,645 participants in the UK Biobank, a large biomedical database and resource to scientists.
Olink, a part of Thermo Fisher Scientific in Waltham, Mass., explains on its website that PEA technology “uniquely combines specificity and scalability to enable high-throughput, multiplex protein biomarker analysis.”
The researchers also compared proteins of people “who did and did not go on to be diagnosed with cancer” to determine differences and identify proteins that suggest cancer risk, News Medical reported.
Proteins Could Assist in Cancer Prevention
“To save more lives from cancer, we need to better understand what happens at the earliest stages of the disease. Data from thousands of people with cancer has revealed really exciting insights into how the proteins in our blood can affect our risk of cancer. Now we need to study these proteins in depth to see which ones could be reliably used for cancer prevention,” Keren Papier, PhD, senior nutritional epidemiologist at Oxford Population Health and joint lead author of the study, told News Medical.
While further studies and regulatory clearance are needed before the Oxford researchers’ approach to identifying cancer in its early stages can be used in patient care, their study highlights scientists’ growing interest in finding biomarker combinations that can predict or diagnose cancer even when it is presymptomatic. By focusing on proteins rather than DNA and RNA, researchers are turning to a source of information other than human genes.
For anatomic pathologists and clinical laboratory leaders, the Oxford study demonstrates how scientific teams are rapidly developing new knowledge about human biology and proteins that are likely to benefit patient care and diagnostics.
Trend will likely lead to physicians ordering more clinical laboratory screening tests for cancer among all age groups, including young patients
Upticks in colorectal cancer cases among younger populations, as reported in recent news stores, is an issue that has implications for clinical laboratories. According to a study conducted at the University of Missouri-Kansas City (UMKC), the number of colorectal cancer cases in the US has increased greatly since 1999 with the “most dramatic jumps” seen in children, teens, and young adults, a Digestive Disease Week (DDW) news release reported.
“Colorectal cancer is no longer considered just a disease of the elderly population,” said lead researcher Islam Mohamed, MD, an internal medicine resident physician at UMKC. “It’s important that the public is aware of signs and symptoms of colorectal cancer.”
The researchers noted in the DDW news release that “colorectal cancer cases, over about two decades, increased by 500% among children, ages 10 to 14; 333% in teens, ages 15 to 19; and 185% among young adults, ages 20 to 24.”
“[The results of the UMKC study] means that there is a trend. We don’t know what to make of it yet. It could be lifestyle factors or genetics, but there is a trend,” lead researcher Islam Mohamed, MD (above), Internal Medicine Resident, University of Missouri-Kansas City, told NBC News. If proved, this trend could lead to increased demand for clinical laboratory screening tests for colorectal and other cancers among young people. (Photo copyright: Digestive Disease Week.)
0.6/100,000 children ages 10 to 14 (a 500% increase).
1.3/100,000 teens ages 15 to 19 (a 333% increase).
Two/100,000 young adults ages 20 to 24 (a 185% increase).
Albeit small numbers, the cases are growing at a rate that is troublesome, according to experts. As NBC put it, “any increase can take on a larger significance” when rates begin at low points.
The study also found incidence of colorectal cancer up in people in their 30s and 40s, reaching by 2020:
6.5/100,000 people ages 30 to 34 (a 71% increase).
11.7/100,000 people ages 35 to 39 (a 58% increase).
20/100,000 people ages 40 to 44 (a 37% increase).
Screening Guidelines May Need to Change
Further research based on UMKC’s study findings could lead to changes in cancer screening guidelines.
“We were screening people from the age of 60 for colon cancer. This has now been lowered to 55, and that is due to be lowered again to 50 over the next few months,” Jude Tidbury, RN, nurse endoscopist and clinical nurse specialist, gastroenterology and endoscopy, at the UK’s East Sussex Healthcare NHS Trust, told Healthline.
In the US, the American Cancer Society advises people of average risk for cancer to start screening for colorectal cancer at age 45. The test options ACS recommends annually include:
What is behind early-onset colorectal cancer among certain age groups? An international study led by Fred Hutchinson Cancer Center (Fred Hutch), Seattle, found “strong correlations” with consuming alcohol and being obese with early-onset colorectal cancer in adults under age 50, according to a news release.
The researchers set out to explore the common genetic variants and causal modifiable risk factors that are behind early-onset colorectal cancer, according to a paper they published in the journal Annals of Oncology.
To do so they used big databases, pulling out 6,176 early-onset colorectal cancer cases and 65,829 controls from sources including:
They focused on “lifestyle factors increasing risk” by comparing the genetic variations in those with colorectal cancer to healthy people, the Fred Hutch news release explained.
“It’s important to see that alcohol and obesity are linked to early-onset colorectal cancer. Also, insulin signaling and infection-related biological pathways. These are all really important to understand—it’s helping us to develop interventions,” said Ulrike Peters, PhD, Professor and Associate Director, Public Health Services Division, Fred Hutch, who co-led the research, in the news release.
Peters noted future research may aim to address data gaps relating to racial and ethnic groups.
More Colorectal Cancer Tests
As studies continue to explore the notion that cancer may not be a disease of aging,
clinical laboratories could see more primary care physicians and healthcare consumers using colorectal cancer screening tests, which require analysis and reporting by labs.
Medical laboratory leaders may want to proactively encourage lab sales and service representatives to educate physician office staff about using the lab’s available resources for screening young adults for colorectal cancer.
Study shows that computer analysis of clinical laboratory test results has improved greatly in recent years
Studies using “big data” continue to show how combining different types of healthcare information can generate insights not available with smaller datasets. In this case, researchers at Washington University School of Medicine (WashU Medicine), St. Louis, Mo., determined that—by using the results from nine different types of clinical laboratory tests—they could correlate those test results to younger people who had “aged faster” and had developed cancer earlier than usual, according to CNN.
“Accumulating evidence suggests that the younger generations may be aging more swiftly than anticipated, likely due to earlier exposure to various risk factors and environmental insults. However, the impact of accelerated aging on early-onset cancer development remains unclear,” said Ruiyi Tian, PhD candidate at WashU Medicine’s Yin Cao Lab in an American Association for Cancer Research (AACR) news release.
The scientists presented their findings, which have not yet been published, at the AACR’s annual meeting held in April. Tian and the other researchers “hypothesized that increased biological age, indicative of accelerated aging, may contribute to the development of early-onset cancers, often defined as cancers diagnosed in adults younger than 55 years. In contrast to chronological age—which measures how long a person has been alive—biological age refers to the condition of a person’s body and physiological processes and is considered modifiable,” AACR noted in a news release.
“We all know cancer is an aging disease. However, it is really coming to a younger population. So, whether we can use the well-developed concept of biological aging to apply that to the younger generation is a really untouched area,” Yin Cao, ScD MPH (above), associate professor of surgery and associate professor of medicine at Washington University School of Medicine in St. Louis, and senior author of the study, told CNN. Analysis of clinical laboratory test results using computer algorithms continues to show value for new research into deadly diseases. (Photo copyright: Washington University.)
Lab Tests Share Insights about Aging
To acquire the data they needed for their research, the WashU Medicine scientists turned to the UK Biobank, a biomedical and research resource with genetic and health information on half a million UK residents.
The researchers reviewed the medical records of 148,724 biobank participants, age 37 to 54, focusing on nine blood-based biomarkers that “have been shown to correlate with biological age,” CNN reported. Those biomarkers are:
White blood cells: counts in “the high end of the normal range” may relate to “greater age.”
According to CNN, the researchers “plugged” the nine values into an algorithm called PhenoAge. Using the algorithm they compared the biological ages with each person’s actual chronological age to determine “accelerated aging.” They then consulted cancer registries to capture data on those in the study who were diagnosed with cancer before age 55. They found 3,200 cases.
Young Adults Aging Faster than Earlier Generations
According to the AACR news release, the WashU Medicine study found that:
“Individuals born in or after 1965 had a 17% higher likelihood of accelerated aging than those born between 1950 and 1954.
“Each standard deviation increase in accelerated aging was associated with a 42% increased risk of early-onset lung cancer, a 22% increased risk of early-onset gastrointestinal cancer, and a 36% increased risk of early-onset uterine cancer.
“Accelerated aging did not significantly impact the risk of late-onset lung cancer (defined here as cancer diagnosed after age 55), but it was associated with a 16% and 23% increased risk of late-onset gastrointestinal and uterine cancers, respectively.”
“We speculate that common pathways, such as chronic inflammation and cellular senescence, may link accelerated aging to the development of early-onset cancers,” the study’s principal investigator Yin Cao, ScD, MPH, associate professor of surgery and associate professor of medicine at WashU Medicine, told The Hill.
“Historically, both cancer and aging have been viewed primarily as concerns for older populations. The realization that cancer, and now aging, are becoming significant issues for younger demographics over the past decades was unexpected,” Tian told Fox News.
More Screenings, Further Analysis
The study’s results may suggest a change in clinical laboratory screenings for younger people.
In future studies, WashU Medicine scientists may aim to include groups of greater diversity and explore why people are aging faster and have risk of early-onset cancers.
“There is room to improve using better technologies. Looking at the bigger picture, the aging concept can be applied to younger people to include cancers, cardiovascular disease, and diabetes,” Cao told Discover Magazine.
While more research is needed, use of the UK’s Biobank of healthcare data—including clinical laboratory test results—enabled the WashU Medicine researchers to determine that accelerated aging among young adults is happening with some regularity. This shows that capabilities in computer analysis are gaining more refined capabilities and are able to tease out insights impossible to achieve with earlier generations of analytical software.
These findings should inspire clinical laboratory professionals and pathologists to look for opportunities to collaborate in healthcare big data projects involving their patients and the communities they serve.
With further study, this research may provide clinical laboratories with a new proteomic biomarker for dementia screenings that identifies risk more than 10 years before symptoms appear
Researchers at the University of Warwick in the UK and Fudan University in Shanghai, China, identified four protein biomarkers in blood that they say can predict dementia up to 15 years before diagnosis. They say these biomarkers may lead to clinical laboratory blood tests that offer alternatives to costly brain scans and lumbar punctures for diagnosis of dementia.
The scientists “used the largest cohort of blood proteomics and dementia to date,” according to a University of Warwick news release. This included taking blood from 52,645 “healthy” people without dementia who participated in the UK Biobank—a population-based study cohort, the new release noted.
“The proteomic biomarkers are [easy] to access and non-invasive, and they can substantially facilitate the application of large-scale population screening,” said neurovegetative disease specialist Jin-tai Yu, MD, PhD, a professor at Fudan University and co-author of the study, in the news release.
“The advent of proteomics offers an unprecedented opportunity to predict dementia onset,” the researchers wrote.
“This is a well-conducted study that adds to what we know about changes in blood that occur very early in diseases that cause dementia, which will be important for early diagnosis in the future,” said Tara Spires-Jones, PhD, in a post from the Science Media Center in the UK. “However,” she added, “it is important to note that these are still scientific research studies and that there are currently no blood tests available for routine use that can diagnose dementia with certainty.
“Based on this study, it does seem likely that blood tests will be developed that can predict risk for developing dementia over the next 10 years, although individuals at higher risk often have difficulty knowing how to respond,” Suzanne Schindler, MD, PhD (above), told Reuters. Schindler, an Associate Professor of Neurology at Washington University in St. Louis, was not involved in the research. Clinical laboratories may soon have a new blood test for dementia. (Photo copyright: VJDementia.)
Predicting Onset of Dementia with 90% Accuracy
The researchers analyzed 52,645 blood samples from the UK Biobank (UKBB). The samples were collected between 2006 and 2010 from healthy individuals who at that time were without dementia.
By March 2023, 1,417 of the study participants had developed Alzheimer’s disease or some other form of dementia. The researchers looked at 1,463 proteins and identified four that were present in high levels among those people:
“Individuals with higher GFAP levels were 2.32 times more likely to develop dementia,” the researchers wrote in Nature Aging. “Notably, GFAP and LTBP2 were highly specific for dementia prediction. GFAP and NEFL began to change at least 10 years before dementia diagnosis.”
When adding known risk factors such as age, sex, and genetics, the researchers said they could predict onset of dementia with 90% accuracy, according to the University of Warwick news release.
“Our findings strongly highlight GFAP as an optimal biomarker for dementia prediction, even more than 10 years before the diagnosis, with implications for screening people at high risk for dementia and for early intervention,” the researchers wrote.
The news release also noted that smaller studies had already identified some of the proteins as potential biomarkers, “but this new research was much larger and conducted over several years.”
Further Validation Needed
Amanda Heslegrave, PhD, of the UK Dementia Research Institute, University College London described the UKBB as “an excellent resource” in the Science Media Center (SMC) post. However, she noted, it’s “a highly curated biobank and may not capture all populations that we need to know the risk for. The new biomarkers identified will need further validation before being used as screening tools.”
Another expert raised additional questions about the University of Warwick/Fudan University study in the SMC post.
“These results may help researchers understand the biological systems involved in the development of dementia,” said David Curtis, MD, PhD, of the UCL Genetics Institute at University College London. “However in my view the strengths of the reported associations are not really strong enough to say that these would form a useful test for predicting who will get dementia in the future.”
Conversely, Curtis pointed to other studies suggesting that phosphorylated tau (p-tau) proteins are better candidates for developing a simple blood test.
P-tau “provides a very good indicator of whether the pathological processes leading to Alzheimer’s disease are present in the brain,” he said. “When effective treatments for Alzheimer’s disease are developed it will be very helpful indeed to have simple blood tests—such as measuring phosphorylated tau—available in order to identify who could benefit.”
At least two blood tests based on the p-tau217 variant—from ALZpath and C2N—are currently available to US clinicians as laboratory developed tests (LDT).
The UK Biobank continues to be used by researchers both in the UK and abroad because of the full sets of data on large numbers of patients over many years. There are few other sources of such data elsewhere in the world. The UK Biobank is a large-scale biomedical database and research resource. It contains de-identified genetic, lifestyle and health information, and biological samples from 500,000 UK participants.
On its website, the UK Biobank states, “It is the most comprehensive and widely-used dataset of its kind and is globally accessible to approved researchers who are undertaking health-related research that is in the public interest, whether they are from academic, commercial, government or charitable settings.”
Thus, clinical laboratory managers and pathologists can expect a continuing stream of published studies that identify biomarkers associated with different health conditions and to see where the data used in these analyses came from the UK’s biobank.
