Bacteria could become new biomarker for testing patients’ reaction to cancer treatments which would give microbiologists and clinical laboratories a new tool for aiding diagnosis and in the selection of appropriate therapies
In a surprising study conducted at King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, British scientists have discovered that a common bacteria found in the mouth may be able to “melt” certain cancers. The bacteria could also be used as a clinical laboratory biomarker to determine how patients may react to specific cancer treatments.
The researchers found that the presence of Fusobacterium can help neutralize head and neck cancers and provide better outcomes in patients with those diseases, according to a Kings College London news release.
“In essence, we found that when you find these bacteria within head and neck cancers, [patients] have much better outcomes,” said Miguel Reis Ferreira, MD, PhD, clinical oncologist at Guy’s and St Thomas’, adjunct senior clinical lecturer at King’s College London and senior author of the study, in the news release. “The other thing that we found is that in cell cultures this bacterium is capable of killing cancer.”
“This research reveals that these bacteria play a more complex role than previously known in their relationship with cancer—that they essentially melt head and neck cancer cells,” said Miguel Reis Ferreira, MD, PhD (above), clinical oncologist at Guy’s and St Thomas’, adjunct senior clinical lecturer at King’s College London and senior author of the study, in a news release. “However, this finding should be balanced by their known role in making cancers such as those in the bowel get worse.” Should these findings prove sound, clinical laboratories may soon have a new biomarker for testing patients’ reaction to cancer treatments. (Photo copyright: King’s College London.)
Researchers Surprised by Their Findings
The researchers began their research by using computer modeling to identify the types of bacteria to further scrutinize. They then studied the effect of those bacteria on cancer cells by analyzing data on 155 head and neck cancer patients whose tumor information had been submitted to the Cancer Genome Atlas. Head and neck cancers include cancers of the mouth, throat, voice box, nose, and sinuses.
The scientists placed Fusobacterium in petri dishes and kept the bacteria there for a few days. They observed the effect of that bacteria on head and neck cancers and discovered there was a 70% to 90% reduction in the number of viable cancer cells after being infused with the Fusobacterium.
Due to the known correlation between Fusobacterium and colorectal cancer, the team was astonished to find the cancer cells present in head and neck cancers had almost been eradicated.
In the news release, Ferreira said the researchers initially expected the Fusobacterium to boost the growth of the cancers and render those cancers more resistant to treatments like radiotherapy. However, they found the opposite to be true.
“The research in colorectal cancer indicates that these bacteria are bad, and that was kind of ingrained into our minds, and we were expecting to find the same thing,” said Ferreira in a Press Association (PA) interview, The Independent reported. “When we started finding things the other way around, we were brutally surprised.”
Predicting Better Outcomes, Lower Risk of Death
“You put it in the cancer at very low quantities and it just starts killing it very quickly,” Ferreira said in the King’s College London news release. “What we’re finding is that this little bug is causing a better outcome based on something that it’s doing inside the cancer. So we are looking for that mechanism at present, and it should be the theme for a new paper in the very short-term future.”
In addition, the scientists discovered that patients with Fusobacterium within their cancer showed improved survival rates when compared to those without the bacteria. The presence of the bacteria correlated with a 65% reduction in death risk.
“What it could mean is that we can use these bacteria to better predict which patients are more likely to have good or worse outcomes, and based on that, we could change their treatment to make it kinder in the patients that have better outcomes or make it more intense in patients that are more likely to have their cancers come back,” said Ferreira in the PA interview.
“Our findings are remarkable and very surprising. We had a eureka moment when we found that our international colleagues also found data that validated the discovery,” said Anjali Chander, PhD student, senior clinical research fellow, Comprehensive Cancer Center, King’s College London, and lead author of the study in the news release.
More to Learn about Bacteria as Biomarkers
According to the National Cancer Institute (NCI), more than 71,000 people will be diagnosed with one of the major types of head and neck cancer this year in the US and more than 16,000 patients will die from these diseases.
The Global Cancer Observatory (GLOBOCAN) estimates there are about 900,000 new cases of head and neck cancers diagnosed annually worldwide with approximately 450,000 deaths attributed to those cancers every year. GLOBOCAN also claims head and neck cancers are the seventh most common cancer globally.
More research and studies are needed to confirm the virtue of this latest venture into the human microbiome. However, the preliminary results of this study appear promising.
The study of human microbiota continues to bring unexpected surprises, as scientists gain more insights and identify specific strains of bacteria that may have a positive or negative influence on an individual’s health. These discoveries may give microbiologists and clinical laboratories intriguing new biomarkers that could be incorporated into medical tests that aid diagnosis and the selection of appropriate therapies.
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.
List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
Although it is a non-specific procedure that does not identify specific health conditions, it could lead to new biomarkers that clinical laboratories could use for predictive healthcare
Researchers from the Mayo Clinic recently used artificial intelligence (AI) to develop a predictive computational tool that analyzes an individual’s gut microbiome to identify how a person may experience improvement or deterioration in health.
Dubbed the Gut Microbiome Wellness Index 2 (GMWI2), Mayo’s new tool does not identify the presence of specific health conditions but can detect even minor changes in overall gut health.
Built on an earlier prototype, GMWI2 “demonstrated at least 80% accuracy in differentiating healthy individuals from those with any disease,” according to a Mayo news release. “The researchers used bioinformatics and machine learning methods to analyze gut microbiome profiles in stool samples gathered from 54 published studies spanning 26 countries and six continents. This approach produced a diverse and comprehensive dataset.”
“Our tool is not intended to diagnose specific diseases but rather to serve as a proactive health indicator,” said senior study author Jaeyun Sung, PhD (above), a computational biologist at the Mayo Clinic Center for Individualized Medicine: Microbiomics Program in the news release ease. “By identifying adverse changes in gut health before serious symptoms arise, the tool could potentially inform dietary or lifestyle modifications to prevent mild issues from escalating into more severe health conditions, or prompt further diagnostic testing.” For microbiologists and clinical laboratory managers, this area of new knowledge about the human microbiome may lead to multiplex diagnostic assays. (Photo copyright: Mayo Clinic.)
Connecting Specific Diseases with Gut Microbiome
Gut bacteria that resides in the gastrointestinal tract consists of trillions of microbes that help regulate various bodily functions and may provide insights regarding the overall health of an individual. An imbalance in the gut microbiome is associated with an assortment of illnesses and chronic diseases, including cardiovascular issues, digestive problems, and some cancers and autoimmune diseases.
To develop GMWI2, the Mayo scientists provided the machine-learning algorithm with data on microbes found in stool samples from approximately 8,000 people collected from 54 published studies. They looked for the presence of 11 diseases, including colorectal cancer and inflammatory bowel disease (IBS). About 5,500 of the subjects had been previously diagnosed with one of the 11 diseases, and the remaining people did not have a diagnosis of the conditions.
The scientists then tested the efficacy of GMWI2 on an additional 1,140 stool samples from individuals who were diagnosed with conditions such as pancreatic cancer and Parkinson’s disease, compared with those who did not have those illnesses.
The algorithm gives subjects a score between -6 and +6. People with a higher GMWI2 score have a healthier microbiome that more closely resembles individuals who do not have certain diseases.
Likewise, a low GMWI2 score suggests the individual has a gut microbiome that is similar to those who have specific illnesses.
Highly Accurate Results
According to their study, the researchers determined that “GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence,” they wrote in Nature Communications.
Launched in 2020, the original GMWI (Gut Microbiome Wellness Index) was trained on a much smaller number of samples but still showed similar results.
The researchers tested the enhanced GMWI2 algorithm across various clinical schemes to determine if the results were similar. These scenarios included individuals who had previous fecal microbiota transplants and people who had made dietary changes or who had exposure to antibiotics. They found that their improved tool detected changes in gut health in those scenarios as well.
“By being able to answer whether a person’s gut is healthy or trending toward a diseased state, we ultimately aim to empower individuals to take proactive steps in managing their own health,” Sung said in the news release.
The Mayo Clinic team is developing the next version of their tool, which will be known as the Gut Microbiome Wellness Index 3. They plan to train it on at least 12,000 stool samples and use more sophisticated algorithms to decipher the data.
More research and studies are needed to determine the overall usefulness of Mayo’s Gut Microbiome Wellness Index and its marketability. Here is a world-class health institution disclosing a pathway/tool that analyzes the human microbiome to identify how an individual may be experiencing either an improvement in health or a deterioration in health.
The developers believe it will eventually help physicians determine how patients’ conditions are improving or worsening by comparing the patients’ microbiomes to the profiles of other healthy and unhealthy microbiomes. As this happens, it would create a new opportunity for clinical laboratories to perform the studies on the microbiomes of patients being assayed in this way by their physicians.
Clinical laboratory executives and pathology leaders may want to develop strategies for supporting the growing numbers of at-home screening and diagnostic test users
Findings of a national poll conducted by the University of Michigan (U-M) exploring consumers’ purchases suggests seniors are becoming more comfortable with ordering and using at-home medical testing. Their choice of tests and opinions may be of interest to clinical laboratory executives, pathologists, and primary care physicians considering programs to support self-test purchasers.
The researchers found that 48% of adults, ages 50 to 80, purchased at least one at-home medical test, and that 91% of the buyers indicated intentions to purchase another test in the future, according to a U-M news release.
In their paper, they note that “validity, reliability, and utility of at-home tests is often uncertain.” Further, understanding and responding to test results—especially since caregivers may not have ordered them—could lead to “a range of unintended consequences,” they wrote.
“As a primary care doctor, I would want to know why my patient chose to take an at-home test that I didn’t order for them. We also need to understand in greater detail why folks use at-home tests instead of traditional means, beyond convenience,” said the U-M study’s lead author Joshua Rager, MD, a research scientist at William M. Tierney Center for Health Services Research at Regenstrief Institute, who is now an assistant professor of medicine, Indiana University, in a news release. The findings of the U-M study will be of interest to clinical laboratory executives and pathology leaders. (Photo copyright: Regenstrief Institute.)
Free COVID-19 Tests Ignite At-Home Testing
In their Journal of Health Care paper, the U-M researchers speculate that curiosity in at-home testing may have been propelled by the offer of free COVID-19 tests by the US government starting in 2021 during the pandemic.
They also noted the different ways at-home test kits are performed by healthcare consumers. Some, such as COVID-19 rapid antigen tests, return results to users in a few moments similar to pregnancy tests. Others involve self-collecting specimens, such as a stool sample, then sending the specimen to a clinical laboratory for analysis and results reporting to physicians.
Of those older adults who participated in U-M’s National Poll on Healthy Aging study, the following bought at-home medical tests online or from pharmacies and supermarkets, according to U-M’s paper:
As to perceptions of at-home medical testing by users, when polled on their test experience, the surveyed seniors reported the following:
75.1% perceived at-home medical tests to be more convenient than conventional medical tests.
59.9% believe the tests “can be trusted to give reliable results.”
54.8% believe the tests “are regulated by government.”
66% called them a “good value.”
93.6% indicated results “should be discussed with my doctor.”
Inconsistency in how people shared test results with their healthcare providers was a concern voiced by the researchers.
“While nearly all patients who had bought an at-home cancer screening test shared the results with their primary care provider, only about half of those who tested for an infection other than COVID-19 had. This could have important clinical implications,” the researchers wrote in their paper.
Confusion over Government Regulation
The U-M study also revealed consumer misunderstanding about government regulation of at-home clinical laboratory tests purchased over-the-counter.
The US Food and Drug Administration (FDA) cleared “some diagnostic at-home tests for over-the counter use. But many tests on the market are unregulated or under-regulated,” the authors wrote, adding, “Our results suggest, however, that patients generally believe at-home tests are regulated by government, but a substantial minority did not, which may reflect public confusion in how at-home testing is regulated.”
Women, College-Educated Buy More At-Home Tests
Purchase of at-home tests varies among groups, as follows, the news release noted:
56% and 61% of older adults with a college degree or household income above $100,000, respectively, were “much more likely” to buy at-home tests than people in other income and education brackets.
87% of women would buy at-home tests again compared with 76% of men.
89% of college-educated people would purchase the tests again, compared with 78% of people with high school educations or less.
Future U-M research may explore consumers’ awareness/understanding concerning federal regulations of at-home testing, Rager noted.
“At-home tests could be used to address disparities in access to care. We hope these findings will inform regulators and policymakers and spark future research on this topic,” he said in the news release.
The U-M Institute for Healthcare Policy and Innovation survey results confirm that the country’s senior generations are becoming comfortable with at-home and self-testing options. As Dark Daily has previously suggested, clinical laboratories may want to develop service offerings and a strategy for supporting patients who want to perform their own lab tests at home.
