Fungi associated with tumors may predict worse cancer outcomes

Certain fungal species in tumors may be associated with worse cancer outcomes, according to a study conducted by researchers at Weill Cornell Medicine and Duke University and published in the journal Cell.

“These findings represent exciting possibilities for future research,” Iliyan Iliev, PhD, associate professor of immunology in medicine in the division of gastroenterology and hepatology and a member of Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, told Healio.

Producing toxins, preventing healing

Iliev characterized some of his earlier work on the effect of fungus on disease outcomes in the setting of inflammatory bowel disease.

“The disease type we investigated in the beginning was a form of inflammatory bowel disease called ulcerative colitis,” Iliev said. “We found that Candida albicans strains isolated from some of the patients produced a toxin called candidalysin. In mouse models, we found that those strains were causing damage and preventing healing in response to corticostreoid therapies.”

When Iliev’s team learned that a higher percentage of these patients with ulcerative colitis developed cancer, they conducted further analysis through The Cancer Genome Atlas, one of the largest genomic databases of human tumors.

“The TCGA database contains primary and metastatic tumors from patients who underwent surgeries, and whole-genome sequencing on these tumors was performed,” he said. “Furthermore, transcription profiles were conducted on these tumors, and proteomics was conducted to assess different proteins.”

Identifying fungus in tumors

The study identified DNA of certain fungal species to be fairly abundant in some tumor types. For example, gastrointestinal tumors contained DNA from Candida tropicalis and Candida albicans, yeast that causes thrush and infections, while lung tumors may be populated by species of the fungal genus Blastomyces. Breast tumors may contain DNA from the fungal genus Malassezia.

As the researchers evaluated these tumors for different fungal and bacterial species, Iliev and Anders Dohlman, a doctoral student in biomedical engineering at Duke University, became suspicious that some of the fungal DNA was related to contamination and genomic “misalignments.”

“We looked at brain tumors and there was fungal and bacterial DNA, including DNA from edible mushrooms,” he said. “We knew that if grew in the brain of a person, especially an immunocompromised person on therapy, they basically would be dead. Even more suspicious was how an edible mushroom would get into a human brain.”

The researchers then created computational methods of excluding fungal DNA that originated from contamination or was a result of a false alignment.

“The premise here was that if you have fungal DNA in samples that are known to be sterile, and you don’t have a record for infection in these patients, then you can develop an algorithm that will tell you if this is actually a contaminant,” he said.

After ruling out fungal DNA that was likely related to contamination, the researchers could confirm the existence of live Candida species in colorectal tumor samples.

The study showed an association between higher levels of Candida species in the tumors and tumor gene activity that triggers inflammation and decreases cell-to-cell adhesion. These factors are known to be linked to cancer metastasis.

The study offered a scientific premise for developing tests to identify specific fungal species associated with tumors that may be predictive of cancer progression.

“These data implicate specific ambers of the mycobiota in association with GI cancers and suggest that tumor-associated fungal DNA may one day serve as a diagnostic or prognostic biomarker,” Iliev said.

The researchers plan to further study the association of fungi and tumors, and specifically will investigate whether specific fungus itself drives tumor progression or whether advanced tumors provide an environment conducive to fungal growth.

For more information :

Iliyan Iliev, PhD, can be reached at Weill Cornell Medicine Iliev Lab, 413 E. 69th St., BB-752, New York, NY 10021; email: ili2001@med.cornell.edu.