4.8 Article

A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors

Journal

CELL
Volume 185, Issue 20, Pages 3807-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2022.09.015

Keywords

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Funding

  1. US National Institutes of Health [R01DK113136, R01DK121977, R01AI163007]
  2. Leona M. and Harry B. Helmsley Charitable Trust
  3. Irma T. Hirschl Career Scientist Award
  4. Research Corporation for Science Advancement Award
  5. Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease (PATH)
  6. Cancer Research Institute Lloyd J. Old STAR Award
  7. Ning Fan of the Molecular Cytology Core at MSKCC [P30 CA008748]
  8. National Institutes of Health [R35GM122465, DK119795, NIHU01CA214300]

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Fungal microorganisms, particularly Candida, play a significant role in the pathogenesis of gastrointestinal cancers, including lung, stomach, and colon cancers. Their presence is associated with immune response, metastatic disease, and decreased survival, suggesting that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.
Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human micro -biome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites re-vealed tumor-associated mycobiomes at up to 1 fungal cell per 104 tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of pro-inflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.

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