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.
Findings could lead to new clinical laboratory cancer screening tests for BRCA1 and BRCA2 among specific population regions
Descendants of a remote Scottish island are much more likely to carry a cancer-causing BRCA2 gene than the rest of the UK. That’s according to a study conducted by the University of Edinburgh in Scotland. For pathologists and clinical laboratory managers, the study’s findings demonstrate how ongoing research into the genetic makeup of subpopulations will find groups that have higher risk for specific health conditions than the general population. Thus, diagnosticians can pay closer attention to screening these groups to achieve early diagnosis and intervention.
“The findings follow earlier research from the Viking Genes study that found a cancer-causing variant in the related BRCA1 gene, common among people from Orkney [a group of islands off Scotland’s northern coast],” noted a University of Edinburgh news release.
In their latest research, the genetic scientists discovered that the BRCA2 gene can be found in one in every 40 people with heritage from the island of Whalsay in Scotland’s Shetland island group. This gene is one of the most common genes that can be linked to breast cancer and ovarian cancer in women and breast and prostate cancer in men.
Those who inherit the BRCA2 gene have a significantly higher risk of developing certain cancers than the general population. For example, according to the National Cancer Institute, more than 60% of women who inherit the gene will develop breast cancer in their lifetimes.
The volunteers in the Viking Genes study have a risk of having a BRCA2 gene that is 130 times higher than the general UK population. According to the BBC, geneticists believe the gene can be traced back to one family from the island of Whalsay before 1750.
“It is very important to understand that just two gene changes account for more than 90% of the inherited cancer risk from BRCA variants in Orkney and Shetland. This is in stark contrast to the situation in the general UK population, where 369 variants would need to be tested to account for the same proportion of cancer risk from BRCA genes. Any future screening program for the Northern Isles should therefore be very cost-effective,” said James Wilson, DPhil, FRCPE (above), Professor of Human Genetics at University of Edinburgh and leader of the study, in a news release. Clinical laboratories in the UK will be involved in those screenings. (Photo copyright: Scottish Genomes Partnership.)
Early Diagnosis Brings Hope to Families
The UK’s National Health Service (NHS) offers genetic testing to relatives of people with a known BRCA variant. Individuals with at least one Whalsay grandparent, and who have a close family history of breast, ovarian, or prostate cancer, can also request NHS testing.
As the BBC reported, University of Edinburgh’s discovery has given families answers and hope for the future. Individuals who fit the criteria for being at risk of inheriting the BRCA gene can narrow their testing and work more specifically on preventative measures with their doctors.
Christine Glaser, a woman from Lerwick in Shetland, learned she carried the BRCA gene after participating in the study. Though the Viking genes research took place nearly a decade ago, scientific understanding of genes has improved allowing geneticists to draw new conclusions from previous studies.
Although Glaser lost her sister to ovarian cancer, she and her family were unaware of their heightened genetic risk.
“I got offered preventative measures so I could get my ovaries removed and I could get a mastectomy. So, that’s what I did … when I got my ovaries removed, they checked them and there was no cancer, but then I had a mammogram and they found cancer,” she told the BBC. Glaser’s cancer was successfully treated thanks to early detection.
Closing Gap in Genetic Testing
“This BRCA2 variant in Whalsay I think arose prior to 1750. This is why these things become so common in given places because many people descend from a couple quite far back in the past, and if they have a cancer variant, then a significant number of people today—five or even 10 generations later—will have it. This is true everywhere in Scotland, it’s just magnified in these small places,” said James Wilson, DPhil, FRCPE, Professor of Human Genetics at University of Edinburgh, who led the study on Viking genes that found individuals with familial ties to two small Scottish communities may be at a higher risk of having a cancer-causing gene.
Wilson hopes to see testing for these genetic abnormalities become more common for these at-risk communities.
“The Ashkenazi Jewish community have BRCA1 and BRCA2 variants that also have a frequency of about one in 40,” he told the BBC. “The Ashkenazi Jewish population in England are able to take part in genetic testing for these genes but that’s not yet the case in Scotland.”
The findings of the most recent University of Edinburgh genetic study are very new. Future developments and offerings from the NHS may be influenced by the results.
Deeper understanding about the genetic make-up of certain population subgroups could lead to new genetic personalized medicine and preventative testing for those at risk of hereditary cancer. In turn, it could also encourage individuals to seek preventative care earlier. Thus, pathologists and clinical laboratory managers should keep an eye on these developments and be prepared to work with geneticists who may develop new screening methods for BRCA1 and BRCA2.
Study findings could lead to new clinical laboratory diagnostics that give pathologists a more detailed understanding about certain types of cancer
New studies proving artificial intelligence (AI) can be used effectively in clinical laboratory diagnostics and personalized healthcare continue to emerge. Scientists in the UK recently trained an AI model using machine learning and deep learning to enable earlier, more accurate detection of 13 different types of cancer.
DNA stores genetic information in sequences of four nucleotide bases: A (adenine), T (thymine), G (guanine) and C (cytosine). These bases can be modified through DNA methylation. There are millions of DNA methylation markers in every single cell, and they change in the early stages of cancer development.
One common characteristic of many cancers is an epigenetic phenomenon called aberrant DNA methylation. Modifications in DNA can influence gene expression and are observable in cancer cells. A methylation profile can differentiate tumor types and subtypes and changes in the process often come before malignancy appears. This renders methylation very useful in catching cancers while in the early stages.
However, deciphering slight changes in methylation patterns can be extremely difficult. According to the scientists, “identifying the specific DNA methylation signatures indicative of different cancer types is akin to searching for a needle in a haystack.”
Nevertheless, the researchers believe identifying these changes could become a useful biomarker for early detection of cancers, which is why they built their AI models.
“Computational methods such as this model, through better training on more varied data and rigorous testing in the clinic, will eventually provide AI models that can help doctors with early detection and screening of cancers,” said Shamith Samarajiwa, PhD (above), Senior Lecturer and Group Leader, Computational Biology and Genomic Data Science, Imperial College London, in a news release. “This will provide better patient outcomes.” With additional research, clinical laboratories and pathologists may soon have new cancer diagnostics based on these AI models. (Photo copyright: University of Cambridge.)
The researchers then used a combination of machine learning and deep learning techniques to train an AI algorithm to examine DNA methylation patterns of the collected data. The algorithm identified and differentiated specific cancer types, including breast, liver, lung and prostate, from non-cancerous tissue with a 98.2% accuracy rate. The team evaluated their AI model by comparing the results to independent research.
In their Biology Methods and Protocols paper, the authors noted that their model does require further training and testing and stressed that “the important aspect of this study was the use of an explainable and interpretable core AI model.” They also claim their model could help medical professionals understand “the underlying mechanisms that contribute to the development of cancer.”
Using AI to Lower Cancer Rates Worldwide
According to the Centers for Disease Control and Prevention (CDC), cancer ranks as the second leading cause of death in the United States with 608,371 deaths reported in 2022. The leading cause of death in the US is heart disease with 702,880 deaths reported in the same year.
Globally cancer diagnoses and death rates are even more alarming. World Health Organization (WHO) data shows an estimated 20 million new cancer cases worldwide in 2022, with 9.7 million persons perishing from various cancers that year.
The UK researchers are hopeful their new AI model will help lower those numbers. They state in their paper that “most cancers are treatable and curable if detected early enough.”
More research and studies are needed to confirm the results of this study, but it appears to be a very promising line of exploration and development of using AI to detect, identify, and diagnose cancer earlier. This type of probing could provide pathologists with improved tools for determining the presence of cancer and lead to better patient outcomes.
Scientists turned to metabolomics to find cause of biological aging and release index of 25 metabolites that predict healthy and rapid agers
Researchers at the University of Pittsburg Medical Center and the University of Pittsburgh School of Medicine have identified biomarkers in human blood which appear to affect biological aging (aka, senescence). Since biological aging is connected to a person’s overall condition, further research and studies confirming UPMC’s findings will likely lead to a new panel of tests clinical laboratories can run to support physicians’ assessment of their patients’ health.
UPMC’s research “points to pathways and compounds that may underlie biological age, shedding light on why people age differently and suggesting novel targets for interventions that could slow aging and promote health span, the length of time a person is healthy,” according to a UPMC news release.
“We decided to look at metabolites because they’re very dynamic,” Aditi Gurkar, PhD, the study’s senior author, told the Pittsburgh Post-Gazette. Gurkar is Assistant Professor of Medicine, Division of Geriatric Medicine, Aging Institute at the University of Pittsburg. “They can change because of the diet, they can change because of exercise, they can change because of lifestyle changes like smoking,” she added.
The scientists identified 25 metabolites that “showed clear differences” in the metabolomes of both healthy and rapid agers. Based on those findings, the researchers developed the Healthy Aging Metabolic (HAM) Index, a panel of metabolites that predicted healthy agers regardless of gender or race.
“Age is more than just a number,” said Aditi Gurkar, PhD (above), Assistant Professor of Geriatric Medicine at University of Pittsburg School of Medicine and the study’s senior author in a news release. “Imagine two people aged 65: One rides a bike to work and goes skiing on the weekends and the other can’t climb a flight of stairs. They have the same chronological age, but very different biological ages. Why do these two people age differently? This question drives my research.” Gurkar’s research may one day lead to new clinical laboratory tests physicians will order when evaluating their patients’ health. (Photo copyright: University of Pittsburg.)
Clear Differences in Metabolites
According to the National Cancer Institute, a metabolite is a “substance made or used when the body breaks down food, drugs, or chemicals, or its own tissue (for example, fat or muscle tissue). This process, called metabolism, makes energy and the materials needed for growth, reproduction, and maintaining health. It also helps get rid of toxic substances.”
The UPMC researchers used metabolomics—the study of chemical process in the body that involves metabolites, other processes, and biproducts of cell metabolism—to create a “molecular fingerprint” of blood drawn from individuals in two separate study groups.
They included:
People over age 75 able to walk a flight of stairs or walk for 15 minutes without a break, and
People, age 65 to 75, who needed to rest during stair climbing and walk challenges.
The researchers found “clear differences” in the metabolomes of healthy agers as compared to rapid agers, suggesting that “metabolites in the blood could reflect biological age,” according to the UPMC news release.
“Other studies have looked at genetics to measure biological aging, but genes are very static. The genes you’re born with are the genes you die with,” said Gurkar in the news release.
Past studies on aging have explored other markers of biological age such as low grade-inflammation, muscle mass, and physical strength. But those markers fell short in “representing complexity of biological aging,” the UPMC study authors wrote in Aging Cell.
“One potential advantage of metabolomics over other ‘omic’ approaches is that metabolites are the final downstream products, and changes are closely related to the immediate (path) physiologic state of an individual,” they added.
The researchers used an artificial intelligence (AI) model that could identify “potential drivers of biological traits” and found three metabolites “that were most likely to promote healthy aging or drive rapid aging. In future research, they plan to delve into how these metabolites, and the molecular pathways that produce them, contribute to biological aging and explore interventions that could slow this process,” the new release noted.
“While it’s great that we can predict biological aging in older adults, what would be even more exciting is a blood test that, for example, can tell someone who’s 35 that they have a biological age more like a 45-year-old,” Gurkar said. “That person could then think about changing aspects of their lifestyle early—whether that’s improving their sleep, diet or exercise regime—to hopefully reverse their biological age.”
Looking Ahead
The UPMC scientists plan more studies to explore metabolites that promote healthy aging and rapid aging, and interventions to slow disease progression.
It’s possible that the blood-based HAM Index may one day become a diagnostic tool physicians and clinical laboratories use to aid monitoring of chronic diseases. As a commonly ordered blood test, it could help people find out biological age and make necessary lifestyle changes to improve their health and longevity.
With the incidence of chronic disease a major problem in the US and other developed countries, a useful diagnostic and monitoring tool like HAM could become a commonly ordered diagnostic procedure. In turn, that would allow clinical laboratories to track the same patient over many years, with the ability to use multi-year lab test data to flag patients whose biomarkers are changing in the wrong direction—thus enabling physicians to be proactive in treating their patients.
Lack of regular clinical laboratory screenings in this age group at least partially to blame, researchers say
While cervical cancer rates have seen a 50-year decline overall, that trend is shifting among 30- to 40 year-olds who have experienced a near 2% increase from 2012-2019. This finding comes from a 2024 American Cancer Society (ACS) report that is eyeing the timeline of the human papillomavirus (HPV) vaccines and the lack of clinical laboratory cancer screenings as possible contributors to this new trend.
Though a 2% increase is significant, the study, which was published in CA: ACancer Journal for Clinicians, titled “Cancer Statistics, 2024,” noted that these cancers were “mostly early, curable tumors,” epidemiologist Ahmedin Jemal DVM, PhD, Senior Vice President Surveillance and Health Equity Science at ACS, and senior author of the new report, told NBC News.
To understand how the increase in cancer rates impacts this age group, consider the numbers: “About 13,800 American women are diagnosed with cervical cancer each year and 4,360 die from the disease,” NBC reported.
US vaccination programs for youths have lagged behind nations that have embraced HPV vaccination to positive results.
Australia, for example, has vaccinated a high proportion of its youth since the vaccine was first released in 2006. In 2023, the nation created its National Strategy for the Elimination of Cervical Cancer in Australia program and expects cervical cancer to be fully eliminated there by 2035.
For lab professionals, this demonstrates how new technologies like the HPV test and vaccine can alter how individuals are screened for diseases, and how vaccines can reduce and even eliminate diseases that were once common.
“We need to make sure we are not forgetting about that generation that was a little too old for HPV vaccination,” Jennifer Spencer, PhD (above), Assistant Professor, Department of Population Health and Department Internal Medicine, Dell Medical School, University of Texas at Austin, told NBC News. “The onus is on the healthcare system to think about who is slipping through the cracks,” she added. Lack of clinical laboratory screenings among the 30-40 age group may be contributing to the increase in cervical cancer rates. (Photo copyright: Dell Medical School.)
Lack of Clinical Laboratory Screenings
Research points to a lag in cervical cancer screenings as a possible cause for the recent rise in cases. Timely screening allows doctors to both identify and remove any worrisome lesions before they become cancerous, Jennifer Spencer, PhD, Assistant Professor of the Department of Population Health, Dell Medical School, University of Texas at Austin, told NBC News.
Screenings for women ages 21-65 have fallen 15% since 2000, according to data from the National Cancer Institute. Also, more than half of women with cervical cancer have “either never been screened or haven’t been screened in the past five years, according to the Centers for Disease Control and Prevention,” NBC reported.
The US Preventative Services Task Force recommends that women 21-29 years of age should receive Pap smears every three years. Women 30-65 years of age should do the same, or every five years with an HPV test or combo test.
Despite a decrease in cervical cancer, 29% of women in their 20s are overdue to get screening, NBC noted. This was the age group most likely to be lagging on getting screened. Spencer says that this delay in screening could explain the resulting increase in cervical cancer among the 30-40 age group.
Causes for Lack in Screenings
Regardless of age group, women who were uninsured, in a rural area, non-white, or identifying as lesbian, bisexual, or gay were also more likely to be overdue on screenings, according to Spencer’s study.
In addition, women who just moved to the United States may have missed their screenings, thus increasing risk, epidemiologist Nicholas Wentzensen, MD, PhD, Deputy Director, Senior Investigator, and Head of the Clinical Epidemiology Unit at the National Cancer Institute, told NBCNews.
Additionally, Spencer found in her research that confusion exists by both patients and doctors on when cervical screening should take place. Some participants in her study did not have screening recommended by their doctors, while others simply did not recognize it was necessary.
“When women in one of Spencer’s studies were asked why they hadn’t been screened recently, they commonly said that they didn’t know they needed to be screened or that a health provider hadn’t recommended it. Only 1% [of] women ages 21 to 29 said they had skipped screening because they had received the HPV shot,” NBC News reported.
A 2022 Journal of American Medicine (JAMA) report also looked at screenings as a possible cause. Those researchers found that “only 73% of women with abnormal screening results received follow-up care,” NBC reported.
“If the increase (in cases) is real, it could be a result of missed screening opportunities at earlier ages, as suggested by the increase in squamous cell carcinoma and localized disease. It may also stem from a decrease in screening at younger ages,” the JAMA study authors wrote.
HPV Vaccine and Cervical Cancer Prevention
The HPV vaccine is another important area of research to be considered. Approved in 2006, HPV vaccines were beneficial because HPV “causes six types of cancer, including cervical cancer,” NBC reported.
Women in their early 20s at that time were the first generation to benefit from HPV vaccines, NBC noted. It may be that they continue to benefit in a decrease in cervical cancer among their cohort.
Countries that have emphasized HPV vaccines and stringent screenings in their cancer prevention efforts are reaping the benefits of that policy.
Though cancer screening and the HPV vaccine are important first steps women should take to prevent cervical cancer, follow-through clinical laboratory testing and diagnosis is crucial, Spencer added. This would include additional testing and treatment for any abnormal results of the cancer screening.
However, according to Spencer, “only 73% of women with abnormal screening results received follow-up care,” NBC reported.
Healthcare policymakers today are emphasizing the need for providers to identify and close gaps in care as a way to improve patient outcomes and help control the cost of care. Women who are overdue for a cervical cancer screening test—whether an HPV test or Pap smear—have this care gap. This creates an opportunity for clinical labs to add value.
Clinical laboratories could be helpful during this period by looking at patient files to note which patients are overdue for screenings and then alerting their doctors. Medical labs also could work directly with doctors to establish a program to reach out to patients. Labs would thus be adding value as well as benefitting patients.
