Promising results showcase benefits of MCED lab tests and provide hope for continued advancements
In impressive new research, Johns Hopkins School of Medicine has developed a clinical laboratory blood test that detects the presence of cancer years before symptoms present, aiding physicians with early diagnosis and treatment.
The identification of cancer cells comes via bloodstream analysis showing genetic materials shed by tumors and showcases the promise of multicancer early detection screening (MCED) to spot all types of cancer in early stages.
“Three years earlier provides time for intervention. The tumors are likely to be much less advanced and more likely to be curable,” Yuxuan Wang, MD, PhD, lead researcher and assistant professor of oncology at Johns Hopkins, told SciTechDaily.
Kimmel Cancer Center, Ludwig Center, the Bloomberg School of Public Health also participated in the study with the support of the National Institutes of Health (NIH).
Senior study author Nickolas Papadopoulos, PhD, professor of oncology at Johns Hopkins School of Medicine and senior author of the study, notes that an appropriate course of clinical care will be required following any positive result from the new cancer diagnostic blood test. (Photo copyright: Johns Hopkins.)
Johns Hopkins Study Details
To complete their research, the scientists studied plasma samples that came from the NIH study on Atherosclerosis Risk in Communities (ARIC), which was created to examine cardiovascular disease risk factors in heart failure, strokes, and heart attacks, SciTechDaily reported.
The researchers analyzed the samples using “highly accurate and sensitive sequencing techniques to analyze blood samples from 26 participants in the ARIC study who were diagnosed with cancer within six months after sample collection, and 26 from similar participants who were not diagnosed with cancer, ” SciTechDaily noted.
At the time of sample gathering, eight of the study participants had received a positive score on the MCED test. Six of them provided additional blood samples dating back 3.1 to 3.5 years. Four of those samples showed mutations, SciTechDaily reported.
Value of MCED Screening
While the sample size in the Johns Hopkins study is small, results of the tests give patients and their physicians a head start on identifying appropriate treatments and demonstrate the strides already made with MCED screening.
MCED tests are relatively new, and while they continue to lack FDA-approval, their ability to discern various types of cancer and provide advanced detection with helpful results make them a promising approach to early cancer screening, the American Cancer Society (ACS) notes.
“For cancers of all stages, therapies are more effective with a lower disease burden,” the scientists wrote in Cancer Discovery.
MCED tests use blood, saliva, urine, or other body fluids to seek out cancer signs through RNA, DNA, or proteins from abnormal cells that may be cancerous. Current screening can assist with cervical, breast, colorectal, prostate, or lung cancer, the ACS added.
Spotting Cancer Earlier
The Johns Hopkins scientist believe detection beyond three years early is likely. “In four of these six participants, the same mutations detected by the multicancer early detection test could be identified, but at 8.6- to 79-fold lower mutant allele fractions. These results demonstrate that it is possible to detect [circulating tumor DNA] more than three years prior to clinical diagnosis and provide benchmark sensitivities required for this purpose,” the Cancer Discovery study notes.
“Detecting cancers years before their clinical diagnosis could help provide management with a more favorable outcome,” Nickolas Papadopoulos, PhD, professor of oncology at Johns Hopkins School of Medicine and senior author of the study, told SciTechDaily.
“Of course, we need to determine the appropriate clinical follow-up after a positive test for such cancers,” he added.
Findings could reduce the need for self-reporting in future nutritional studies and lead to new clinical laboratory testing
Clinical laboratory testing may one day influence whether a person snacks on a bag of chips every day or chooses to eat healthy foods instead.
Researchers at the National Institutes of Health (NIH) reported that they have identified biomarkers in blood and urine that can indicate an individual’s consumption of ultra-processed foods (UPF).
Scientists discovered a signature that is predictive of a dietary pattern that’s high in ultra-processed food, study leader Erikka Loftfield, PhD, MPH, epidemiologist and principal investigator with the NIH, told the Associated Press (AP).
Using data on the biomarkers—metabolites left after the body breaks down food—the researchers devised a “poly-metabolite score” that could potentially “reduce the reliance on, or complement the use of, self-reported dietary data in large population studies,” according to an NIH press release.
This will be helpful because, according to the AP, “Typical nutrition studies rely on recall: asking people what they ate during a certain period. But such reports are notoriously unreliable because people don’t remember everything they ate, or they record it inaccurately.”
“Limitations of self-reported diet are well known. Metabolomics provides an exciting opportunity to not only improve our methods for objectively measuring complex exposures like diet and intake of ultra-processed foods, but also to understand the mechanisms by which diet might be impacting health,” said Loftfield in the press release.
Thus, it’s conceivable that one day clinical laboratory testing could affect people’s food choices and help to improve their health.
“There’s a need for both a more objective measure and potentially also a more accurate measure,” Erikka Loftfield, PhD, MPH, epidemiologist and principal investigator with the NIH, told the Associated Press. (Photo copyright: National Cancer Institute.)
Study Methodology
The findings were based in part on an earlier study of 718 AARP members, aged 50-74, who agreed to submit blood and urine samples. The participants also completed dietary recall reports.
“The researchers found hundreds of metabolites that correlated with the percentage of energy from ultra-processed foods in the diet,” the NIH press release noted. “Using machine learning, researchers identified metabolic patterns associated with high intake of ultra-processed foods and calculated poly-metabolite scores for blood and urine separately.”
To test their findings, the researchers referred to a 2019 NIH study involving 20 adults aged 18 to 50. Under carefully controlled conditions, these participants spent two weeks consuming high levels of ultra-processed foods, followed by two weeks consuming no ultra-processed foods. As with the AARP cohort, they also submitted blood and urine samples. The poly-metabolite score proved to be an accurate measure of which diets they had consumed, the researchers reported.
The researchers acknowledged limitations in the study that will necessitate further research. “Study participants were older US adults whose diets may vary from other populations,” the authors noted. “Poly-metabolite scores should be evaluated and iteratively improved in populations with diverse diets and a wide range of UPF intake.”
Ultra-Processed Foods Defined
The NIH defines ultra-processed foods as “ready-to-eat or ready-to-heat, industrially manufactured products, typically high in calories and low in essential nutrients.” Diets high in these foods have been associated with “increased risk of obesity and related chronic diseases, including some types of cancer,” the press release noted.
In identifying these foods, the researchers cited a 2019 paper published in the journal Public Health Nutrition (PHN). The paper relied on the NOVA classification system, which makes a distinction between “processed” and “ultra-processed” foods. The latter typically contain “food substances never or rarely used in kitchens,” or cosmetic additives “whose function is to make the final product palatable or more appealing,” the PHN paper noted.
“From sugary cereals at breakfast to frozen pizzas at dinner, plus in-between snacks of potato chips, sodas and ice cream, ultra-processed foods make up about 60% of the US diet,” the AP reported in an earlier story. “For kids and teens, it’s even higher—about two-thirds of what they eat.”
Discovery could lead to new clinical laboratory testing for cancer screening in new mothers
Any clinical laboratory test that returns unexpected results is worth looking into more deeply. Such was the case with a recent study conducted by the National Institutes of Health (NIH), which investigated cases of pregnant women who received “unusual” results to prenatal lab tests conducted at a dozen labs in North America.
Following cancer screening protocols that included rapid whole-body magnetic resonance imaging, NIH scientists discovered “previously undetected cancers in 48.6% of pregnant people who had abnormal results for prenatal cell-free DNA (cfDNA) testing used to screen for chromosomal disorders in the fetus,” according to an NIH news release.
“They looked like healthy young women, and they reported themselves as being healthy,” Diana Bianchi, MD, head of the Prenatal Genomics and Therapy Section for the Medical Genetics Branch at the NIH’s National Human Genetics Research Institute, and senior author of the government study, told the Associated Press (AP).
While cfDNA tests are not diagnostic, pathologists and clinical laboratory managers involved in genetic testing are likely familiar with them. The blood tests are used by expectant mothers to assess risk of a fetus with an abnormal number of chromosomes that could suggest disorders such as Down Syndrome, according to ARUP Laboratories.
Unexpected results from tests draw attention. This one seems to have a chance to get more traction with labs because the results point to a prenatal test having some success predicting cancer, even if incidentally.
“[The study participants] and their care providers need to take the results seriously and have additional testing because in that population there is a 48% risk of cancer,” Diana Bianchi, MD, senior author of the NIH study, told the AP. (Photo copyright: National Institutes of Health.)
Cancer Found in about Half of Those with Abnormal cfDNA
The NIH researchers started a long-term study, called IDENTIFY, to learn more about abnormal cfDNA results that could suggest cancer. Study participants must be:
Pregnant or postpartum with no known cancer.
Recipients of “unusual clinical cfDNA-sequencing results or results that are non-reportable (fetal aneuploidy status could not be assessed) from one of 12 different commercial laboratories,” they wrote in NEJM.
For the study’s initial cohort of 107 participants, researchers repeated cfDNA sequencing testing and coordinated standard medical diagnostic tests (such as Pap smears) and whole-body magnetic resonance imaging.
52 women (48.6%) were found to have “hidden cancers.”
32 had blood cancers.
20 had solid tumors in the breast, bile duct, colon, pancreas, lung, kidney, bone, and adrenal gland.
13 of the 20 with solid tumors were able to access “potentially curative treatments.”
55 women did not have cancer and may have obtained an unreliable cfDNA result.
“In this study, 48.6% of participants who received unusual or nonreportable clinical cfDNA-sequencing results had an occult cancer (cancer of unknown primary).
“Further study of DNA-sequencing patterns that are suggestive of occult cancer during prenatal screening is warranted,” the researchers wrote in NEJM.
Follow-Up Testing Needed
Cancers found in the study participants “included colorectal, breast, lung and pancreatic cancers, as well as lymphoma, cholangiocarcinoma and renal carcinoma. The screening test analyzes placental DNA fragments circulating in the maternal bloodstream to identify an extra chromosome or to determine the baby’s sex,” according to the NIH news release.
Bianchi told AP the study results also pointed to a “very chaotic” pattern in DNA-sequencing of women with cancer, and that more research is needed to find out who should be screened for cancer.
Clinical laboratories and pathologists who analyze cfDNA tests could take a leadership role in assessing current standards for the tests, determining how suspicious results are reported, and suggesting needed changes.
With more study, the technique could lead to new precision medicine pathology diagnostics and clinical laboratory tests
Researchers at Yale University have devised a new pathology tool that utilizes barcode technology to map the spatial relationships of ribonucleic acid (RNA) and proteins. This will be of interest to histopathologists who are responsible for examining clinical laboratory tissue samples and helping physicians diagnose disease.
Called Patho-DBiT (pathology-compatible deterministic barcoding in tissue), the Yale scientists claim their new tool can completely examine RNA and possibly aid in the diagnoses and treatment of cancer.
The technology, according to a Yale news release, “is unique in that it has microfluidic devices that deliver barcodes into the tissue from two directions creating a unique 2D ‘mosaic’ of pixels, providing spatial information that could be used to inform the creation of patient-specific targeted therapies.”
“It’s the first time we can directly ‘see’ all kinds of RNA species, where they are and what they do, in clinical tissue samples,” said Rong Fan, PhD, Harold Hodgkinson professor of biomedical engineering and pathology at Yale and senior author of the study.
“I think it’s going to completely transform how we study the biology of humans in the future,” said Rong Fan, PhD (above), Harold Hodgkinson professor of biomedical engineering and pathology at Yale and senior author of the study, in a Yale news release. The discovery could lead to new clinical laboratory screening tests and diagnostics for cancer. (Photo copyright: Yale University.)
More Precise Cancer Diagnoses
“As a physician who has been diagnosing cancer, I was surprised by how much more I can see using this pathology tool,” said Mina Xu, MD, professor of pathology at Yale School of Medicine and one of the authors of the study. “I think this deep molecular dive is going to advance our understanding of tumor biology exponentially. I really look forward to delivering more precise and actionable diagnoses.”
According to the Yale study, the Patho-DBiT tool has many beneficial capabilities. They include:
Dissecting spatiotemporal dynamics of lymphomagenesis at the single-cell level.
FFPE tissue involves the fixation of tissues by utilizing formalin and embedding tissue samples in paraffin wax. This method allows for the long-term preservation of tissue morphology and cellular details and is commonly used in histopathology.
In the past, the RNA within FFPE samples have been susceptible to fragmentation during the paraffin-embedding process and degradation issues. These samples may also experience chemical modifications which could result in resistance to the enzymatic reactions necessary for proper sequencing.
“There are millions of these tissues that have been archived for so many years, but up until now, we didn’t have effective tools to investigate them at spatial level,” said the study’s first author Zhiliang Bai, PhD, a postdoctoral associate in Rong Fan’s lab at Yale. “RNA molecules in these tissues we’re looking at are highly fragmented and traditional methods can’t capture all the important information about them. It’s why we’re very excited about Patho-DBiT.”
Targeted Therapies
The team is encouraged by their research and the future potential for Patho-DBiT. They believe the technology may be useful in creating targeted therapies and helping understand the metamorphosis of low-grade tumors to more aggressive ones. They conceive their tool may assist in developing ways to prevent the progression of cancers.
“It is very exciting that Patho-DBiT-seq is also capable of generating spatial maps of noncoding RNA expression,” said Jun Lu, PhD, associate professor of genetics at Yale and another of the study’s authors. “Noncoding RNAs are often in regions of our genomes that were previously thought of as junk DNA, but now they are recognized as treasured players in biology and diseases such as cancer.”
The research included faculty members from several departments at Yale and was supported by the National Institutes of Health (NIH). The technology is now licensed to biotechnology company AtlasXomics of New Haven, Ct., for further development.
More research and studies are needed to validate the findings of this research, but the Patho-DBiT tool could prove to be useful for the preservation of tissue samples and become essential in the diagnoses and treatment of cancers.
The NIH’s Researching COVID to Enhance Recovery (RECOVER) Initiative used a cohort study of more than 10,000 individuals with and without previous COVID-19 diagnoses and compared samples using 25 common laboratory tests in hopes a useful biomarker could be identified. They were unsuccessful.
Long COVID—or PASC—is an umbrella term for those with persistent post-COVID infection symptoms that negatively impact quality of life. Though it affects millions worldwide and has been called a major public health burden, the NIH/Langone study scientists noted one glaring problem: PASC is defined differently in the major tests they studied. This makes consistent diagnoses difficult.
The study brought to light possible roadblocks that prevented biomarker identification.
“This study is an important step toward defining long COVID beyond any one individual symptom,” said study author Leora Horwitz, MD (above), director of the Center for Healthcare Innovation and Delivery Science and co-principal investigator for the RECOVER CSC at NYU Langone, in a Langone Health news release. “This definition—which may evolve over time—will serve as a critical foundation for scientific discovery and treatment design.” In the future, clinical laboratories may be tasked with finding combinations of routine and reference tests that, together, enable a more precise and earlier diagnosis of long COVID. (Photo copyright: Yale School of Medicine.)
NIH/Langone Study Details
“The study … examined 25 routinely used and standardized laboratory tests chosen based on availability across institutions, prior literature, and clinical experience. These tests were conducted prospectively in laboratories that are certified by the Clinical Laboratory Improvement Amendments (CLIA). The samples were collected from 10,094 RECOVER-Adult participants, representing a diverse cohort from all over the US,” Inside Precision Medicine reported.
However, the scientists found no clinical laboratory “value” among the 25 tests examined that “reliably indicate previous infection, PASC, or the particular cluster type of PASC,” Inside Precision Medicine noted, adding that “Although some minor differences in the results of specific laboratory tests attempted to differentiate between individuals with and without a history of infection, these findings were generally clinically meaningless.”
“In a cohort study of more than 10,000 participants with and without prior SARS-CoV-2 infection, we found no evidence that any of 25 routine clinical laboratory values provide a reliable biomarker of prior infection, PASC, or the specific type of PASC cluster. … Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC,” the study authors wrote in Annals of Internal Medicine.
In addition to a vague definition of PASC, the NIH/Langone researchers noted a few other potential problems identifying a biomarker from the research.
“Use of only selected biomarkers, choice of comparison groups, if any (people who have recovered from PASC or healthy control participants); duration of symptoms; types of symptoms or phenotypes; and patient population features, such as sex, age, race, vaccination status, comorbidities, and severity of initial infection,” could be a cause for ambiguous results, the scientists wrote.
Future Research
“Understanding the basic biological underpinnings of persistent symptoms after SARS-CoV-2 infection will likely require a rigorous focus on investigations beyond routine clinical laboratory studies (for example, transcriptomics, proteomics, metabolomics) to identify novel biomarkers,” the study authors wrote in Annals of Internal Medicine.
“Our challenge is to discover biomarkers that can help us quickly and accurately diagnose long COVID to ensure people struggling with this disease receive the most appropriate care as soon as possible,” said David Goff, MD, PhD, director of the division of cardiovascular sciences at the NIH’s National Heart, Lung, and Blood Institute, in an NHLBI news release. “Long COVID symptoms can prevent someone from returning to work or school, and may even make everyday tasks a burden, so the ability for rapid diagnosis is key.”
“Approximately one in 20 US adults reported persisting symptoms after COVID-19 in June 2024, with 1.4% reporting significant limitations,” the NIH/Langone scientists wrote in their published study.
Astute clinical laboratory scientists will recognize this as possible future diagnostic testing. There is no shortage of need.
