Studies could lead to new prognostic biomarkers and clinical laboratory diagnostics for cancer

Might fungi be involved in human cancers? Two separately published studies have found fungal DNA in various cancers in the human body. However, the researchers are unclear on how the fungi got into the cancer cells and if it is affecting the cancers’ pathology. Nevertheless, these discoveries could lead to utilizing tumor-associated fungal DNA as clinical laboratory diagnostics or prognostic biomarkers in the fight against cancer. 

The first study, performed by a team of international researchers from the University of California San Diego (UCSD) and the Weizmann Institute of Science in Israel, detected the presence of fungal DNA or cells in some cancer types.

They published their findings in the peer-reviewed scientific journal Cell, titled, “Pan-cancer Analyses Reveal Cancer-type Specific Fungal Ecologies and Bacteriome Interactions.”  

Ravid Straussman, MD, PhD

“The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens,’” said Ravid Straussman, MD, PhD (above), a principal investigator at Weizmann Institute of Science and one of the authors of the study in a UCSD press release. These findings could lead to new clinical laboratory diagnostics and prognostic biomarkers. (Photo copyright: Weizmann Institute of Science.)

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Microbiome Key to Cancer Biology and Detection

To perform their research, the team examined 17,401 samples of patient tissues, blood, and plasma across 35 different types of cancers in four independent cohorts. They discovered fungal DNA and cells in low abundances in many human cancers. 

“The existence of fungi in most human cancers is both a surprise and to be expected,” said biologist Rob Knight, PhD, founding Director of the Center for Microbiome Innovation and Professor of Pediatrics and Computer Science and Engineering at UC San Diego in a UCSD press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.”

The main highlights of this study include:

  • Fungi detected in the different cancer types were often intracellular.
  • Multiple fungal-bacterial-immune ecologies were detected across tumors.
  • Intratumoral fungi stratified clinical outcomes, including immunotherapy response.
  • Cell-free fungal DNA found in both healthy and cancer patients in early-stage disease.

Fungi found on the human body appear as either environmental fungi, such as yeasts and molds, and commensal fungi, which live either on or inside the body. Both are typically harmless to most healthy people and can provide some benefits, such as improving gut health, but they may also be a contributing factor in some disease.

The researchers found that there were notable parallels between specific fungi and certain factors, such as age, tumor subtypes, smoking status, immunotherapy responses, and survival measures.

“These findings validate the view that the microbiome in its entirety is a key piece of cancer biology and may present significant translational opportunities, not only in cancer detection, but also in other biotech applications related to drug development, cancer evolution, minimal residual disease, relapse, and companion diagnostics,” said Gregory Sepich-Poore, MD, PhD, one of the study’s authors and co-founder and chief analytics officer at biotechnology company Micronoma, in the UCSD press release.  

New Clinical Laboratory Tests to Identify Fungal Species in Cancer

The second study also was published in the journal Cell, titled, “A Pan-cancer Mycobiome Analysis Reveals Fungal Involvement in Gastrointestinal and Lung Tumors.”

Researchers from Duke University and Cornell University uncovered compelling evidence of fungi in multiple cancer types and focused on a detected link between Candida and gastrointestinal cancers.

They found that “several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival,” according to their paper.

Their analysis of multiple body sites revealed tumor-associated mycobiomes in fungal cells. The researchers found that fungal spores known as blastomyces were associated with tumor tissues in lung cancers, and that high rates of Candida were present in stomach and colon cancers.

The Duke/Cornell researchers hope their work can provide a framework to develop new tests that can distinguish fungal species in tumors and predict cancer progression and help medical professionals and patients chose the best treatment therapies. 

“These findings open up a lot of exciting research directions, from the development of diagnostics and treatments to studies of the detailed biological mechanisms of fungal relationships to cancers,” said Iliyan Iliev, PhD, Associate Professor of Microbiology and Immunology in Medicine, Weill Cornell Medicine, and one of the authors of the study, in a Weill news release.

More research is needed to determine if fungal DNA plays a role in disease pathology or if its presence does not have any causal link.

“It’s plausible that some of these fungi are promoting tumor progression and metastasis, but even if they aren’t, they could be very valuable as prognostic indicators,” Iliev said.

The insights gleaned from these two studies will be of particular interest to microbiologists, clinical laboratory professionals, and anatomic pathologists. Additional research could answer questions about how and if fungi infect tumors and if such fungi is a factor that increases cancer risk and outcomes. 

JP Schlingman

Related Information:

Fungal DNA, Cells Found in Human Tumors

First-ever Mycobiome Atlas Describes Associations Between Cancers and Fungi

Pan-cancer Analyses Reveal Cancer-type Specific Fungal Ecologies and Bacteriome Interactions

A Pan-cancer Mycobiome Analysis Reveals Fungal Involvement in Gastrointestinal and Lung Tumors

Fungal Association with Tumors May Predict Worse Outcomes

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