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Impact of Mycobiome on Dysregulation of Inflammasome-related Genes in Head and Neck Squamous Cell Carcinomas and Lung Squamous Cell Carcinomas

Abstract

Cancer continues to be a lethal challenge to human health. While research has uncovered many causes and effects of cancer, the role of the microbiome has been uncovered more recently. Fungi are an integral part of the human mycobiome, yet they have been studied far less than the bacterial microbiome in cancer. Studying the immune response to fungal pathogens is an important endeavor as it can shed light on the fungal landscape in healthy and cancerous tissue. Fungal pathogenesis involves the activation of inflammasomes and is an important aspect of the immune response to fungi. In this study I sought to characterize the fungal mycobiome in head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC), and to elucidate dysregulations of inflammasome-related genes in the two cancers. I used RNA-seq data from TCGA from cancer tissue and adjacent normal tissue, extracted fungal abundance counts, and correlated these with survival, clinical variables, and infiltration of multiple types of immune cells. I also identified correlations between fungal abundance and inflammasome-related genes, and inflammasome-related pathways. I found multiple fungal species to be differentially abundant and correlated with inflammasome-related genes in both HNSC and LUSC including Saccharomyces cerevisiae, Saccharomyces cerevisiae N85, and Kappamyces sp. PL-117. I also found species that were uniquely associated with HNSC or LUSC. These findings characterize the fungal mycobiome and elucidate the correlation between fungal species and inflammasome-related genes in HSNC and LUSC.

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