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Clinical Laboratories and Pathology Groups

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Researchers in China Develop AI-powered Tool That Can Diagnose Three Cancers Using a Drop of Dried Blood

Use of artificial intelligence in clinical laboratory testing could improve the diagnosis of cancer worldwide

In a proof of concept study, scientists at Shanghai Jiao Tong University in China have developed a clinical laboratory test that utilizes artificial intelligence (AI) to diagnose three types of cancer from a single drop of dried blood. The paper-based test was able to identify patients with colorectal, gastric, and pancreatic cancers and distinguish between patients with and without cancer.

The team’s goal was to develop a way to diagnose cancer while the disease is still in the earlier stages, especially in rural areas.

“Over a billion people across the world experience a high rate of missed disease diagnosis, an issue that highlights the need for diagnostic tools showing increased accuracy and affordability. In addition, such tools could be used in ecologically fragile and energy-limited regions, pointing to the need for developing solutions that can maximize health gains under limited resources for enhanced sustainability,” the researchers wrote in an article published in the journal Nature Sustainability titled, “A Sustainable Approach to Universal Metabolic Cancer Diagnosis.”

The researchers determined that by using less than 0.05 millimeters of dried blood, their test could accurately and quickly identify if a patient had cancer between 82% to 100% of the time.

According to Chaoyuan Kuang, MD, PhD (above), an oncologist at Montefiore Health System and assistant professor at the Albert Einstein College of Medicine, unlike liquid blood, dried serum can be “collected, stored, and transported at much lower cost and with much simpler equipment,” Live Science reported. “This could help democratize the availability of cancer early detection testing across the world,” he added. A paper-based clinical laboratory test that can detect and distinguish one cancer type from another would be a boon to cancer diagnosis worldwide. (Photo copyright: Albert Einstein College of Medicine.)

Improving Cancer Screening in Rural Areas

An earlier study conducted in China in 2022 examined results from 1,570 cancer survivors from both urban and rural areas of China. That study showed that 84.1% of the patients were diagnosed with cancer only after developing symptoms and that urban patients were more likely to be diagnosed in the early stages of cancer. In addition, rural patients also had less screening and treatment options available to them.

The researchers in this latest Chinese study tested their AI model on blood donors with and without cancer and compared the results to traditional liquid-blood biopsy tests.

“Based on modeling they performed, they reported the new tool could reduce the estimated proportion of undiagnosed cases of pancreatic, gastric, and colorectal cancers by about 20% to 50% if it was used for population-level cancer screening in rural China,” Live Science reported. 

The scientists used dried serum spots (DSS) and machine learning to perform the research. According to their Nature Sustainability paper, DSS can be challenging in cancer research because sensitive biomarkers in the samples are often degraded or have inadequate amount of blood for proper analysis. To circumvent these issues, the researchers used nanoparticle-enhanced laser desorption/ionization mass spectrometry (NPELDI MS) to increase reliability and sensitivity. Inorganic nanoparticles were applied to the samples to strengthen selectivity and refine metabolic compounds from the samples.

However, the study authors noted that “the adaptation of NPELDI MS to dried spot analysis has not been validated,” Interesting Engineering reported.

A ‘Great Start’

The machine learning algorithm the Chinese scientists created demonstrates that DSS samples can be used to preserve important biological markers and could be beneficial in the diagnosis of cancer. 

Their research indicated an overall reduction rate of undiagnosed cancers in the range of 20.35% to 55.10%. The researchers estimated the implementation of their AI tool could reduce the proportion of specific undiagnosed cancer cases in rural China by:

  • 84.30% to 29.20% for colorectal cancer,
  • 77.57% to 57.22% for gastric cancer, and
  • 34.56% to 9.30% for pancreatic cancer.

It’s a “great start,” Chaoyuan Kuang, MD, PhD, an oncologist at Montefiore Health System and assistant professor at the Albert Einstein College of Medicine told Live Science. “This cancer test won’t enter use for a long time,” he said. Nevertheless, the potential of the tool is “immense,” he added, but that “we are still years away from being able to offer this test to patients. 

“With further development, it could theoretically be used for the early detection of other types of cancer or for other diseases, or to monitor the progression of disease in patients who have already been diagnosed,” he noted.

Further research and clinical trials are needed before this AI tool can be used in a clinical diagnostic setting. This study is another example of researchers looking for cancer biomarkers in specimen types that are not tissue and further supports the hope that machine learning may one day detect cancer in earlier stages, increase survival rates, and save healthcare costs.

One factor motivating this type of research in China is the fact that the nation has more than 36,000 hospitals and approximately 20,000 anatomic pathologists. Of this total, only a minority of these pathologists have been trained to the standards of North America and Northern Europe.

Like other nations, China’s demand for subspecialist pathology services outstrips its supply of such pathologists. This is the reason why researchers in that country want to develop diagnostic assays for cancer and other diseases that are faster, cheaper, and comparable to a human pathologist in accuracy.

—JP Schlingman

Related Information:

Detecting Cancer in Minutes Possible with Just a Drop of Dried Blood and New Test, Study Hints

AI-powered Tool Detects Cancer in Minutes with One Drop of Blood

Dried Blood Spot Testing

A Sustainable Approach to Universal Metabolic Cancer Diagnosis

New Sustainable Diagnostic Approach Offers Precision Cancer Testing with Minimal Environmental Impact

The Urban-Rural Disparities and Associated Factors of Health Care Utilization Among Cancer Patients in China

University Hospitals Birmingham Claims Its New AI Model Detects Certain Skin Cancers with Nearly 100% Accuracy

UK Study Claims AI Reading of CT Scans Almost Twice as Accurate at Grading Some Cancers as Clinical Laboratory Testing of Sarcoma Biopsies

UK’s National Health Service Tests AI Tool That Can Spot Cancer in Mammograms Missed by Doctors

Mayo Clinic Scientists Use Chemical Analysis of Beethoven’s Hair to Determine Lead Poisoning May Have Contributed to Composer’s Hearing Loss and Other Health Ailments

Results of an earlier study in which locks of Beethoven’s hair underwent genetic analysis showed the composer ‘had a predisposition for liver disease and became infected with hepatitis B’

Here is an example of modern technologies being used with “historical biospecimens” to solve long-standing mysteries or questions about the illnesses of famous historical figures. Clinical laboratory scientists at the Mayo Clinic have used modern-day chemical analysis techniques to answer a 200-year-old question: What caused Ludwig van Beethoven’s deafness and other health problems?

In a letter published in Clinical Chemistry, a journal of the Association for Diagnostics and Laboratory Medicine (ADLM) titled, “High Lead Levels in 2 Independent and Authenticated Locks of Beethoven’s Hair,” researchers with the metals laboratory within Mayo’s Division of Clinical Biochemistry and Immunology revealed analysis performed on authenticated locks of the composer’s hair. The results indicated extremely high concentrations of lead—64 to 95 times the expected level.

“Such lead levels are commonly associated with gastrointestinal and renal ailments and decreased hearing but are not considered high enough to be the sole cause of death,” the authors wrote.

Beethoven’s death at age 56 has been attributed to kidney and liver disease, CNN reported. Even if the lead concentrations were not the sole cause, they would nevertheless be regarded as lead poisoning, lead study author Nader Rifai, PhD, told CNN.

“If you walk into any emergency room in the United States with these levels, you will be admitted immediately and you will undergo chelation therapy,” he said.

Rifai is a professor of pathology at Harvard Medical School and director of clinical chemistry at Boston Children’s Hospital.

“It is believed that Beethoven died from liver and kidney disease at age 56. But the process of understanding what caused his many health problems has been a much more complicated puzzle, one that even Beethoven himself hoped doctors could eventually solve,” CNN reported, adding, “The composer expressed his wish that his ailments be studied and shared so ‘as far as possible at least the world will be reconciled to me after my death.’” Mayo clinical laboratory scientists are using chemical analysis on authenticated locks of Beethoven’s hair to do just that. (Photo copyright: Joseph Karl Stieler/Public Domain.)

Mass Spectrometry Analysis

Mayo Clinic’s metals laboratory, led by chemist Paul Jannetto, PhD, an associate professor in the Department of Laboratory Medicine and Pathology and Laboratory Director at the Mayo Clinic, performed the analysis on two authenticated locks of Beethoven’s hair, using inductively coupled plasma mass spectrometers.

The researchers found that one lock had 258 micrograms of lead/gram and the other had 380 micrograms. Normally they would expect to find less than four micrograms.

“These are the highest values in hair I’ve ever seen,” Jannetto told The New York Times. “We get samples from around the world and these values are an order of magnitude higher.”

The researchers also found that the composer’s hair had four times the normal level of mercury and 13 times the normal amount of arsenic.

Rifai and other researchers noted that Beethoven drank large amounts of plumbed wine, and at the time it was common to sweeten wine with lead acetate, CNN reported.

The composer also could have been exposed to lead in glassware. He likely absorbed high levels of arsenic and mercury by eating fish caught from the Danube River in Vienna.

David Eaton, PhD, a toxicologist, pharmacologist, and Professor Emeritus, Department of Environmental and Occupational Health Sciences at the University of Washington, told The New York Times that high levels of lead could have impaired Beethoven’s hearing through their effect on the nervous system. Additionally, he said the composer’s gastrointestinal ailments “are completely consistent with lead poisoning.”

Rifai told CNN that he’d like to study locks of hair from other 19th century Vienna residents to see how their lead levels compared with Beethoven’s.

Beethoven’s Genome and Genetic Predisposition for Liver Disease

Additional research published in May built on an earlier genomic analysis of Beethoven’s hair, which appeared in March 2023 in the journal Current Biology.

The international team included geneticists, archeologists, and immunologists who analyzed eight locks of hair attributed to the composer. They determined that five were authentic. One, known as the Stumpff Lock, appeared to be the best preserved. They used this lock to sequence Beethoven’s DNA.

“Although we could not identify a genetic explanation for Beethoven’s hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease,” the authors wrote. “Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven’s severe liver disease, which culminated in his death.”

One surprising discovery was the likelihood of an extramarital affair on the composer’s father’s side, CNN reported. The researchers learned this in part by comparing his genetic profile with those of living relatives.

“Through the combination of DNA data and archival documents, we were able to observe a discrepancy between Ludwig van Beethoven’s legal and biological genealogy,” study coauthor Maarten Larmuseau, PhD, told CNN. Larmuseau is assistant professor, Faculty of Medicine, and head of the Laboratory of Human Genetic Genealogy at KU Leuven in Belgium.

The Mayo Clinic team used two locks authenticated in the 2023 study—the Bermann Lock and Halm-Thayer Lock—to perform their chemical analysis, CNN reported.

Beethoven’s Wishes

The earlier study noted that Beethoven wanted his health problems to be made public. In 1802, he wrote a document known as the Heiligenstadt Testament in which he asked that his physician, surgeon/ophthalmologist Johann Adam Schmidt, MD, discuss his disease after he died.

“For almost two years I have ceased to attend any social functions, just because I find it impossible to say to people: I am deaf,” Beethoven wrote at age 30, The New York Times reported. “If I had any other profession, I might be able to cope with my infirmity, but in my profession, it is a terrible handicap. And if my enemies, of whom I have a fair number, were to hear about it, what would they say?”

The authors of the Current Biology paper wrote, “Genomic sequence data from authenticated locks of Beethoven’s hair provide Beethoven studies with a novel primary source, already revealing several significant findings relating to Beethoven’s health and genealogy, including substantial heritable risk for liver disease, infection with HBV [Hepatitis B], and EPP [extra pair paternity]. This dataset additionally permits numerous future lines of scientific inquiry.

“The further development of bioinformatics methods for risk stratification and continued progress in medical genetic research will allow more precise assessments both for Beethoven’s disease risk and for the genetic inference of additional phenotypes of interest.

“This study illustrates the contribution and further potential of genomic data as a novel primary source in historical biography,” the scientists concluded.

The work of the clinical laboratory professionals at Mayo Clinic also demonstrates how advances in various diagnostic technologies can enable pathologists and lab scientists to participate in solving long-standing health questions about historical figures, especially if their hair or other types of specimens survived and can be used in the analysis.  

—Stephen Beale

Related Information:

High Lead Levels in 2 Independent and Authenticated Locks of Beethoven’s Hair

Locks of Beethoven’s Hair Offer New Clues to the Mystery of His Deafness

New Analysis of Beethoven’s Hair Reveals Possible Cause of Mysterious Ailments, Scientists Say

Beethoven May Have Had Lead Poisoning

Paul Jannetto, PhD, Contributes to Landmark Discovery of Beethoven’s Hair Lead Concentration

Beethoven Really Did Have Lead Poisoning, But That Didn’t Cause His Death

Genomic Analyses of Hair from Ludwig Van Beethoven

DNA from Beethoven’s Hair Unlocks Medical and Family Secrets

DNA Analysis of Beethoven’s Hair Reveals Health Issues—and a Family Secret

Brigham and Women’s Hospital Researchers Develop Implantable ‘Lab in a Patient’ to Test Effectiveness of Brain Cancer Drugs

Scientists reported positive Phase 1 trial results of their “intratumoral microdevice” in patients with glioma tumors

Here is an example of new microtechnology which has the potential to greatly shorten the time and improve the ability of physicians to determine which anti-cancer drug is most effective for an individual patient’s glioblastoma. As it is further developed, this technology could give anatomic pathologists and clinical laboratories an increased role in assessing the data produced by microdevices and helping physicians determine the most appropriate anti-cancer drug for specific patients.

In a news release, researchers at Brigham and Women’s Hospital (BWH) in Boston said they have developed an implantable “intratumoral microdevice” (IMD) that functions as a “lab in a patient,” capable of gauging the effectiveness of multiple drugs that target brain tumors. In a Phase 1 clinical trial, they tested the IMD on six patients with glioma tumors.

“In order to make the greatest impact on how we treat these tumors, we need to be able to understand, early on, which drug works best for any given patient,” study co-author Pier Paolo Peruzzi, MD, PhD, told the Harvard Gazette. “The problem is that the tools that are currently available to answer this question are just not good enough. So, we came up with the idea of making each patient their own lab, by using a device which can directly interrogate the living tumor and give us the information that we need.”

Peruzzi is Principal Investigator at the Harvey Cushing Neuro-Oncology Laboratories and Assistant Professor of Neurosurgery at Harvard Medical School.

The researchers published their findings in the journal Science Translational Medicine titled, “Intratumoral Drug-Releasing Microdevices Allow In Situ High-Throughput Pharmaco Phenotyping in Patients with Gliomas.” [PHOTO OF PERUZZI HERE

“Our goal is for the placement of these devices to become an integral part of tumor surgery,” said Pier Paolo Peruzzi, MD PhD (above) of Brigham and Women’s Hospital and Harvard Medical School in an article he co-wrote for Healio. “Then, with the data that we have from these microdevices, we can choose the best systemic chemotherapy to give to that patient.” Pathologists and clinical laboratories may soon play a role in helping doctors interpret data gathered by implantable microdevices and choose the best therapies for their patients. (Photo copyright: Dana-Farber Cancer Institute.)

New Perspective on Tumor Treatments

In a news story he co-wrote for Healio, Peruzzi explained that the microdevice—about the size and shape of a grain of rice—contains up to 30 tiny reservoirs that the researchers fill with the drugs they want to test. Surgeons implant the device during a procedure to remove the tumors.

The surgery takes two to three hours to perform, and during that time, the device releases “nanodoses” of the drugs into confined areas of the tumor. Near the end of the procedure, the device is removed along with tissue specimens. The researchers can then analyze the tissue to determine the effectiveness of each drug.

“This is not in the lab, and not in a petri dish,” Peruzzi told Harvard Gazette. “It’s actually in real patients in real time, which gives us a whole new perspective on how these tumors respond to treatment.”

The Healio story notes that gliomas are “among the deadliest brain cancers and are notoriously difficult to treat.” With current approaches, testing different therapies has posed a challenge, Peruzzi wrote.

“Right now, the only way these drugs are tested in patients is through what are called window-of-opportunity studies, where we give one drug to the patient before we resect the tumor and analyze the effect of the drug,” he said. “We can only do this with one drug at a time.”

Determining Safety of Procedure

The primary goal of the Phase 1 trial was to determine the safety of the procedure, Peruzzi noted. “To be in compliance with standard clinical practice and minimize risks to the patients, we needed to integrate the placement and retrieval of the device during an otherwise standard operation.”

The trial consisted of three men and three women ranging from 27 to 86 years old, with a median age of 76. Five were diagnosed with glioblastoma and one with grade 4 astrocytoma.

“None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens,” the researchers wrote in Science Translational Medicine. They noted that application of the IMD added about 32 minutes to the time required for the surgery, equating to a cost increase of $7,800.

One drug they tested was temozolomide (TMZ), “the most widely used agent in this patient population,” they wrote. “Several patients in our trial received it systemically, either before or after IMD insertion, as part of the standard of care. Thus, although our trial was not designed to choose chemotherapy agents based on IMD data, we still could compare the observed clinical-radiological response to systemic TMZ with the patient-specific response to TMZ in the IMD-exposed tissue.”

One patient, the researchers noted, had not benefited from the drug “in concordance with the poor tissue response observed in the IMD analysis.” But in another patient, a 72-year-old woman, “IMD analysis showed a marked response to TMZ,” and she survived for 20 months after receiving the treatment “with radiological evidence of tumor response. This was despite having a subtotal tumor resection, in itself an unfavorable prognostic factor. The patient expired because of an unrelated cardiovascular event, although she had remained neurologically stable.”

Drug Duration Limitation

One limitation of the study was that testing the device during the tumor removal procedure limited the duration of the drug treatments, Peruzzi said. The Harvard Gazette noted that following their initial study, the researchers were testing a variation of the procedure in which the device is implanted three days before the main surgery in a minimally invasive technique. This gives the drugs more time to work.

Cancer researchers have theorized that common treatments for tumors can impair the immune system, Peruzzi wrote in Healio. “One thing we want to look at is which drugs can kill the tumor without killing the immune system as well,” he noted.

Future studies will determine the effectiveness of implanting microdevices into tumors to test therapies in vivo. Should they become viable, clinical laboratories and anatomic pathologists will likely be involved in receiving, interpreting, storing, and transmitting the data gathered by these devices to the patient’s doctors.

—Stephen Beale

Related Information:

Microdevices Implanted into Tumors Offer New Way to Treat Brain Cancer

Intratumoral Drug-Releasing Microdevices Allow In Situ High-Throughput Pharmaco Phenotyping in Patients with Gliomas

Microdevices Turn Brain Tumors into Tiny Labs

Devices Implanted into Brain Tumors During Surgery May Guide Treatment

Human Brain Tumor Implant Could Guide Personalized Therapies Tiny Implanted Devices Give Insights for Treating Brain Tumors

University of Cincinnati Pathologist Develops Speedier Tissue Processing for Small Biopsies

Syringe-based technique is disposable and enables clinical laboratories to process small biopsies in about two hours instead of overnight and with significantly less waste

Histotechnologists and clinical laboratory managers know that the standard method of processing tissue biopsies takes a lot of time and chemical resources and isn’t always efficient. But what if there was a way to process biopsy tissue without the need for large processors that require a large batch of tissue to be economical?

That is what cytopathologist Paul Lee, MD, PhD, Assistant Professor of Clinical Pathology, University of Cincinnati (UC) College of Medicine, asked himself when he set out to design a rapid technique for processing small biopsies.

Lee was inspired to find a way to change the process while completing his residency at the University of Massachusetts, UC News reported.

“I noticed a specific issue with the procedure for fixing and examining tissue samples to look for signs of cancer and other diseases,” Lee told UC News. “And I had this idea.”

His goal was to reduce time to answer for a patient waiting to learn if he/she has cancer.

To achieve this feat, Lee developed a new technique that, according to UC News, “employs a disposable syringe and cuvette to do individual tissue tests, using small paraffin blocks and a combined embedding-fixing process for quick, accurate reads of small biopsies.”

Lee says his technique brings the potential of “immediate reads” closer to reality.

“If that process can take just two hours, not overnight, it becomes an inpatient procedure,” Lee told UC News. “Patients don’t have to go home … and return for a surgery consult, then for surgery itself.

“All that can be arranged in a day or two,” he added. “Patient care won’t be compromised or lost to follow-up.”

Paul Lee, MD, PhD (above), Assistant Professor of Clinical Pathology at University of Cincinnati College of Medicine, compares the development of his new small-biopsy tissue processing technique for histology laboratories and clinical laboratories to the philosophy behind the invention of the Keurig single-serving beverage machine. “Let’s say you’re making a cup of coffee. If you made a whole carafe and only needed one cup, that’d be wasteful—of both time and resources. Think of this as Keurig for specimen processing.” (Photo copyright: University of Cincinnati.)

Simplifying, Accelerating Rapid Tissue Processing

Lee describes the traditional method “coupling large tissue processors with traditional embedding techniques” as “slow and wasteful.” This, he told UC News, is still how tissue processing is done.

“It [uses] huge amounts of solvent, massive paraffin blocks,” he continued, “and [leaves] doctors waiting up to seven hours for results.”

The standard procedure uses “an enormous processor, gallons of solvent, and 300-500 dehydrated specimens embedded in blocks and then cut into slices for slides,” he added.

In addition to the “waste or expense,” the process “prevents physicians from making same-day diagnoses unless they’re willing to destroy precious tissue,” Lee noted.

Lee told UC News that his technique “preserves tissue [and] doesn’t compromise the sample, so we can do ancillary tests to revalidate results … and with the disposable cuvette there’s no chance of cross-contamination. Plus, it can be easily incorporated into existing infrastructure. [It] doesn’t have to upset processes or workflow.”

Lee’s method can also save resources and reduce wait times. “I get requests [from other researchers] all the time for various samples and I have to put a lot of them off for human pathology tests,” Lee said. “They can be their own processors and not wait for results from another lab. It’s quicker for them too and uses fewer resources.”

Other Advantages of Lee’s Method 

Lee’s research team has successfully tested a prototype and they are currently awaiting a patent.

According to UC’s Office of Innovation, advantages of Lee’s new technique for small-biopsy tissue processing include:

  • Rapid, convenient processing.
  • Disposable specimen cuvette (no cross contamination).
  • Antigenicity preservation.
  • Less solvent usage (associated with less cost for solvent disposal).
  • Can be easily incorporated into existing infrastructure.
  • Very small footprint.

“Turn-around times for ‘rapid processing’ using current techniques typically range from four to seven hours, often preventing physicians from making same day diagnosis without destroying precious tissue,” the Office of Innovation noted in a statement. “This often results in delayed diagnosis, additional use of both patient and healthcare resources, and potentially poorer patient outcomes.

“Dr. Paul Lee has developed a novel tissue fixation and embedding system that combines the tissue fixation and embedding process creating a rapid processing block for biological specimens,” UC’s Office of Innovation continued. “The invention dramatically shortens processing and embedding time to approximately two hours while preserving the antigenicity and morphology of the specimen and thus allows for rapid reads of small biopsies in a timeframe that was not previously achievable.”

Lee’s work could streamline tissue processing in histology laboratories and increase efficiency without sacrificing accuracy. Anatomic pathologists and clinical laboratories would be wise to monitor this revolutionary new technology for further developments.

—Ashley Croce

Related Information:

UC Pathologist Designs Rapid Technique For Small Biopsies

Syringe Based Rapid Processor for Small Biopsies

Fred Hutch Researchers Identify Oral Bacteria That Appear to Play a Role in Certain Colon Cancers

Discovery highlights how ongoing microbiome research points to new opportunities that can lead to development of more effective cancer screening clinical laboratory tests

New research from the Fred Hutchinson Cancer Center in Seattle once again demonstrates that the human microbiome plays a sophisticated role in many biological processes. Microbiologists and anatomic pathologists who diagnose tissue/biopsies will find this study’s findings intriguing.

This breakthrough in colon cancer research came from the discovery that a “subspecies” of a common type of a bacteria that resides in the mouth and causes dental plaque also “shields tumor cells from cancer treatment,” according to NBC News.

The scientists inspected colorectal cancer (CRC) tumors and found that 50% of those examined featured a subspecies of Fusobacterium nucleatum (F. nucleatum or Fn) and that this anaerobic bacterium was “shielding tumor cells from cancer-fighting drugs,” NBC News noted. Many of these tumors were considered aggressive cases of cancer. 

“The discovery, experts say, could pave the way for new treatments and possibly new methods of screening,” NBC News reported.

The Fred Hutchinson Cancer Center scientists published their findings in the journal Nature titled, “A Distinct Fusobacterium Nucleatum Clade Dominates the Colorectal Cancer Niche.”

“Patients who have high levels of this bacteria in their colorectal tumors have a far worse prognosis,” Susan Bullman, PhD (above), who jointly supervised the Fred Hutch research team and who is now Associate Professor of Immunology at MD Anderson Cancer Center, told NBC News. “They don’t respond as well to chemotherapy, and they have an increased risk of recurrence,” she added. Microbiologists and clinical laboratories working with oncologists on cancer treatments will want to follow this research as it may lead to new methods for screening cancer patients. (Photo copyright: Fred Hutchinson Cancer Center.)

Developing Effective Treatments

Susan Bullman, PhD, Associate Professor of Immunology at MD Anderson Cancer Center, who along with her husband and fellow researcher Christopher D. Johnston, PhD, Assistant Professor at Fred Hutchinson Cancer Center, jointly supervised an international team of scientists that examined the genomes of 80 F. nucleatum strains from the mouths of cancer-free patients and 55 strains from tumors in patients with colorectal cancer, according to the National Institutes of Health (NIH). The NIH funded the research.

The researchers targeted a subspecies of F. nucleatum called F. nucleatum animalis (Fna) that “was more likely to be present in colorectal tumors. Further analyses revealed that there were two distinct types of Fna. Both were present in mouths, but only one type, called Fna C2, was associated with colorectal cancer” the NIH wrote in an article on its website titled, “Gum Disease-related Bacteria Tied to Colorectal Cancer.”

“Tumor-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumor niche,” the Fred Hutch researchers wrote in their Nature paper.

“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Johnston told the NIH.

How Bacteria Got from Mouth to Colon Not Fully Understood

Traditionally, F. nucleatum makes its home in the mouth in minute quantities. Thus, it is not fully understood how these bacteria travel from the mouth to the colon. However, the Fred Hutch researchers showed that Fna C2 could survive in acidic conditions, like those found in the gut, longer than the other types of Fna. This suggests that the bacteria may travel along a direct route through the digestive tract.

The study, which focused on participants over 50, comes at a time when colorectal cancer rates are trending upward. Rates are doubling for those under 55, jumping from 11% in 1995 to 20% in 2019. CRC is the second-leading cancer death and over 53,000 will succumb to the disease in 2024, according to NBC News.

Many of the newer diagnoses are in later stages with no clear reason why, and the Fred Hutch scientists are trying to understand how their findings tie into the increase of younger cases of colon cancer.

Bullman says it will be important to look at “whether there are elevated levels of this bacterium in young onset colorectal cancer, which is on the rise globally for unknown reasons,” she told NBC News.

Possibility of More Effective Cancer Screening

There is hope that scientists equipped with this knowledge can develop new and more effective screening and treatment options for colon cancer, as well as studying the microbiome’s impact on other diseases.

On the prevention side, researchers have seen that in mice the addition of Fna “appeared to cause precancerous polyps to form, one of the first warning signs of colorectal cancer, though Bullman added that this causation hasn’t yet been proven in humans.” NBC reported.

Future research may find that screening for Fna could determine if colorectal tumors will be aggressive, NIH reported.

“It’s possible that scientists could identify the subspecies while it’s still in the mouth and give a person antibiotics at that point, wiping it out before it could travel to the colon,” Bullman told NBC News. “Even if antibiotics can’t successfully eliminate the bacteria from the mouth, its presence there could serve as an indication that someone is at higher risk for aggressive colon cancer.”

There is also the thought of developing antibiotics to target a specific subtype of bacteria. Doing so would eliminate the need to be “wiping out both forms of the bacteria or all of the bacteria in the mouth. Further, it’s relevant to consider the possibility of harnessing the bacteria to do the cancer-fighting work,” NBC noted.

“The subtype has already proven that it can enter cancer cells quite easily, so it might be possible to genetically modify the bacteria to carry cancer-fighting drugs directly into the tumors,” Bullman told NBC News.

Further studies and research are needed. However, the Fred Hutch researchers’ findings highlight the sophistication of the human microbiome and hint at the potential role it can play in the diagnosis of cancer by clinical laboratories and pathology groups, along with better cancer treatments in the future.

—Kristin Althea O’Connor

Related Information:

A New Type of Bacteria was Found in 50% Of Colon Cancers. Many Were Aggressive Cases.

Gum Disease-related Bacteria Tied to Colorectal Cancer

A Distinct Fusobacterium Nucleatum Clade Dominates the Colorectal Cancer Niche