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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Washington University Researchers Uses Medical Laboratory Test Results and Big Data to Find Accelerated Aging and Risk of Early Cancer in Young Adults

Study shows that computer analysis of clinical laboratory test results has improved greatly in recent years

Studies using “big data” continue to show how combining different types of healthcare information can generate insights not available with smaller datasets. In this case, researchers at Washington University School of Medicine (WashU Medicine), St. Louis, Mo., determined that—by using the results from nine different types of clinical laboratory tests—they could correlate those test results to younger people who had “aged faster” and had developed cancer earlier than usual, according to CNN.

“Accumulating evidence suggests that the younger generations may be aging more swiftly than anticipated, likely due to earlier exposure to various risk factors and environmental insults. However, the impact of accelerated aging on early-onset cancer development remains unclear,” said Ruiyi Tian, PhD candidate at WashU Medicine’s Yin Cao Lab in an American Association for Cancer Research (AACR) news release.

The scientists presented their findings, which have not yet been published, at the AACR’s annual meeting held in April. Tian and the other researchers “hypothesized that increased biological age, indicative of accelerated aging, may contribute to the development of early-onset cancers, often defined as cancers diagnosed in adults younger than 55 years. In contrast to chronological age—which measures how long a person has been alive—biological age refers to the condition of a person’s body and physiological processes and is considered modifiable,” AACR noted in a news release.

“We all know cancer is an aging disease. However, it is really coming to a younger population. So, whether we can use the well-developed concept of biological aging to apply that to the younger generation is a really untouched area,” Yin Cao, ScD MPH (above), associate professor of surgery and associate professor of medicine at Washington University School of Medicine in St. Louis, and senior author of the study, told CNN. Analysis of clinical laboratory test results using computer algorithms continues to show value for new research into deadly diseases. (Photo copyright: Washington University.)

Lab Tests Share Insights about Aging

To acquire the data they needed for their research, the WashU Medicine scientists turned to the UK Biobank, a biomedical and research resource with genetic and health information on half a million UK residents.

The researchers reviewed the medical records of 148,724 biobank participants, age 37 to 54, focusing on nine blood-based biomarkers that “have been shown to correlate with biological age,” CNN reported. Those biomarkers are:

According to CNN, the researchers “plugged” the nine values into an algorithm called PhenoAge. Using the algorithm they compared the biological ages with each person’s actual chronological age to determine “accelerated aging.” They then consulted cancer registries to capture data on those in the study who were diagnosed with cancer before age 55. They found 3,200 cases.

Young Adults Aging Faster than Earlier Generations

According to the AACR news release, the WashU Medicine study found that:

  • “Individuals born in or after 1965 had a 17% higher likelihood of accelerated aging than those born between 1950 and 1954.
  • “Each standard deviation increase in accelerated aging was associated with a 42% increased risk of early-onset lung cancer, a 22% increased risk of early-onset gastrointestinal cancer, and a 36% increased risk of early-onset uterine cancer.
  • “Accelerated aging did not significantly impact the risk of late-onset lung cancer (defined here as cancer diagnosed after age 55), but it was associated with a 16% and 23% increased risk of late-onset gastrointestinal and uterine cancers, respectively.”

“We speculate that common pathways, such as chronic inflammation and cellular senescence, may link accelerated aging to the development of early-onset cancers,” the study’s principal investigator Yin Cao, ScD, MPH, associate professor of surgery and associate professor of medicine at WashU Medicine, told The Hill.

“Historically, both cancer and aging have been viewed primarily as concerns for older populations. The realization that cancer, and now aging, are becoming significant issues for younger demographics over the past decades was unexpected,” Tian told Fox News.

More Screenings, Further Analysis

The study’s results may suggest a change in clinical laboratory screenings for younger people.

“We see cancers earlier all the time now, and nobody knows why. The subset in the population that has accelerated aging may need screening more often or earlier,” Emanuela Taioli, MD, PhD, professor of population health and science and of thoracic surgery, and director of the Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, told Health.

In future studies, WashU Medicine scientists may aim to include groups of greater diversity and explore why people are aging faster and have risk of early-onset cancers. 

“There is room to improve using better technologies. Looking at the bigger picture, the aging concept can be applied to younger people to include cancers, cardiovascular disease, and diabetes,” Cao told Discover Magazine.

While more research is needed, use of the UK’s Biobank of healthcare data—including clinical laboratory test results—enabled the WashU Medicine researchers to determine that accelerated aging among young adults is happening with some regularity. This shows that capabilities in computer analysis are gaining more refined capabilities and are able to tease out insights impossible to achieve with earlier generations of analytical software.

These findings should inspire clinical laboratory professionals and pathologists to look for opportunities to collaborate in healthcare big data projects involving their patients and the communities they serve.

—Donna Marie Pocius

Related Information:

Accelerated Aging May Increase the Risk of Early-onset Cancers in Younger Generations

Accelerated Aging Linked to Cancer Risk in Younger Adults, Research Shows

An Epigenetic Biomarker of Aging for Lifespan and Health Span in Aging

Accelerated Aging May be a Cause of Increased Cancers in People under 55

Cancer Rates Rising in Young People Due to “Accelerated Aging,” New Study Finds

Research Shows Accelerated Aging Linked to Increased Cancer Risk in Younger Adults

Rate of Biological Aging is Accelerating in Young People, Leading to Medical Issues

South Korean Study Finds Fecal Microbiota Transplants May Help Patients with Gastrointestinal Cancers That are Resistant to Immunotherapies

Study findings could lead to improved treatments for broad range of cancers and the need for microbiome testing by clinical laboratories to guide clinicians

Is it possible that there is a connection between an individual’s gut microbiota and the ability to fight off gastrointestinal (GI) cancer? Findings from a preliminary research study performed by researchers in South Korea suggest that a link between the two may exist and that fecal microbiota transplants (FMTs) may enhance the efficacy of immunotherapies for GI cancer patients. 

The proof-of-concept clinical trial, conducted at the Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea, analyzed how an FMT could help 13 patients with metastatic solid tumors that were resistant to the anti-PD-1 antibody drug known as nivolumab (Opdivo). Anti-PD-1 drugs are immunotherapies that help treat cancer by improving an individual’s immune response against cancer cells. 

Four of the trial participants had gastric cancer, five had esophageal cancer, and the remaining four had hepatocellular carcinoma. The patients were given a colonoscopy to implant the FMTs. The recipients also received antibiotics to reduce the response of their existing microbiotas.

The FMT donors also had gastric cancer, esophageal cancer, or hepatocellular carcinoma. Prior to donating their fecal matter, the donors experienced complete or partial response to the anti-PD-1 drugs nivolumab or pembrolizumab (Keytruda) for at least six months after receiving initial treatments. 

The researchers published their study, titled, “Fecal Microbiota Transplantation Improves Anti-PD-1 Inhibitor Efficacy in Unresectable or Metastatic Solid Cancers Refractory to Anti-PD-1 Inhibitor,” in the journal Cell Host and Microbe.

“This research highlights the complex interplay between beneficial and detrimental bacteria within the gut microbiota in determining treatment outcomes,” co-senior study author Hansoo Park, MD, PhD, Assistant Professor, Biomedical Science and Engineering, Gwangju Institute of Science and Technology, told The ASCO Post. “While the connection between gut microbiota and immune response to cancer therapy has been a growing area of interest, our study provides concrete evidence and new avenues for improving treatment outcomes in a broader range of cancers,” he added. Further studies may confirm the need for microbiome testing by clinical laboratories to guide clinicians treating patients with colon cancers. (Photo copyright: Gwangju Institute of Science and Technology.)

Surprising Results

Fecal material for an FMT procedure combines donated fecal matter with a sterile saline solution which is then filtered to produce a liquid solution. That solution is then administered to the recipient via colonoscopy, upper GI endoscopy, enema, or an oral capsule. The solution may also be frozen for later use.

Upon analyzing the recipients, the scientists found that six of the patients (46.2%) who had experienced resistance to immunotherapies for their cancers, benefitted from the FMTs.

“One of the most surprising results was from a [patient with] hepatocellular carcinoma who initially showed no response to the first [FMT] and continued to experience cancer progression. However, after switching the donor for the second [transplant], the patient exhibited remarkable tumor shrinkage,” co-senior study author Sook Ryun Park, MD, PhD, Assistant Professor, Asan Medical Center at the University of Ulsan College of Medicine in Seoul, told The ASCO Post, a journal of the American Society of Clinical Oncology.

“Both donors were long-lasting, good responders to anti-PD-1 inhibitors, but because we did not yet know the causative bacteria responsible for the [FMT] response, we could not predict whether the treatment would be effective,” she added.

The researchers also determined that the presence of a bacterial strain known as Prevotella merdae helped to improve the effectiveness of the FMTs, while two strains of bacteria—Lactobacillus salivarius and Bacteroides plebeius (aka, Phocaeicola plebeius)—had a detrimental impact on the transplants. 

Challenges to Widespread Adoption of FMTs

The researchers acknowledge there are challenges in widespread acceptance and use of FMTs in treating cancers but remain optimistic about the possibilities.

“Developing efficient and cost-effective methods for production and distribution is necessary for widespread adoption,” Sook Ryun Park told The ASCO Post. “Addressing these challenges through comprehensive research and careful planning will be essential for integrating FMT into the standard of care for cancer treatment.”

The research for this study was supported by grants from the Asan Institute for Life Sciences, Asan Medical Center, National Cancer Centre in Korea, the GIST Research Institute, the Bio and Medical Technology Development Program from Ministry of Science, and the Ministry of Science and ICT of the South Korean Government.

More research and clinical trials are needed before this use of FMTs can be utilized in clinical settings. However, the study does demonstrate that the potential benefits of FMTs may improve outcomes in patients with certain cancers. As this happens, microbiologists may gain a new role in analyzing the microbiomes of patients with gastrointestinal cancers.

“By examining the complex interactions within the microbiome, we hope to identify optimal microbial communities that can be used to enhance cancer treatment outcomes,” Hansoo Park told The ASCO Post. “This comprehensive approach will help us understand how the microbial ecosystem as a whole contributes to therapeutic success.”

—JP Schlingman

Related Information:

Fecal Microbiota Transplant May Help Patients with Gastrointestinal Cancers Overcome Immunotherapy Resistance

Fecal Microbiota Transplantation Improves Anti-PD-1 Inhibitor Efficacy in Unresectable or Metastatic Solid Cancers Refractory to Anti-PD-1 Inhibitor

Fecal Microbiota Transplants Can Boost the Effectiveness of Immunotherapy in Gastrointestinal Cancers

When Screening for Esophageal and Gastrointestinal Cancer, Rice University’s Low-Cost Microendoscope Could Reduce Need to Send Biopsies to Pathologists

This low-cost solution opens new doors for low-resource regions and, in many cases, allows operators to rule out malignancy without the need for a pathologist to review biopsies

Rapid development of endoscopic technologies is bringing medical professionals closer to point-of-care pathology than ever before. The goal is to allow physicians to identify diseased or cancerous tissue in situ and reduce or eliminate the need to biopsy tissue for examination by surgical pathologists.

Researchers at Rice University in Houston are developing a high-resolution microendoscope (HRME) that offers the ability to view tissue at a subcellular level. This fiber optic probe would reduce the need to collect the biopsy that is typically sent to anatomic pathologists for analysis.

Measuring 1-mm in diameter, the probe works using the existing accessory channel of the endoscope. Touching it to the surface of the tissue provides real-time in vivo images to the technician at up to 12 frames per second on an accompanying tablet display. Images are enhanced using visual overlays and an algorithm that highlights the nuclei of cells within the field of view. The HRME system is battery powered and fits in a briefcase for easy transport. (more…)

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