Transcriptomic Analysis Reveals Dysregulation of the Mycobiome and Archaeome and Distinct Oncogenic Characteristics according to Subtype and Gender in Papillary Thyroid Carcinoma

Abstract

Papillary Thyroid Carcinoma (PTC) is characterized by unique tumor morphology, treatment response, and patient outcomes according to subtype and gender. While previous studies have implicated the intratumor bacterial microbiome in the incidence and progression of PTC, few studies have investigated the potential role of fungal and archaeal species in oncogenesis. In this study, we aimed to characterize the intratumor mycobiome and archaeometry in PTC with respect to its three primary subtypes: Classical (CPTC), Follicular Variant (FVPTC), and Tall Cell (TCPTC), and also with respect to gender. RNA-sequencing data were downloaded from The Cancer Genome Atlas (TCGA), including 453 primary tumor tissue samples and 54 adjacent solid tissue normal samples. The PathoScope 2.0 framework was used to extract fungal and archaeal microbial read counts from raw RNA-sequencing data. Overall, we found that the intratumor mycobiome and archaeometry share significant similarities in CPTC, FVPTC, and TCPTC, although most dysregulated species in CPTC are underabundant compared to normal. Furthermore, differences between the mycobiome and archaeometry were more significant between males and females, with a disproportionate number of fungal species overabundant in female tumor samples. Additionally, the expression of oncogenic PTC pathways was distinct across CPTC, FVPTC, and TCPTC, indicating that these microbes may uniquely contribute to PTC pathogenesis in each subtype. Furthermore, differences in the expression of these pathways were observed between males and females. Finally, we found a specific panel of fungi to be dysregulated in BRAF V600E-positive tumors. This study demonstrates the potential importance of microbial species to PTC incidence and oncogenesis.

Fungi and cancer

“…All tumour samples featured hybridisation signals compatible with specific fungal genera. Recently, fungal reads extracted from RNA sequencing data were compared between samples of different papillary thyroid carcinoma subtypes, showing differences in species abundance by subtype, sex and compared with healthy controls 73…”

Intratumor microbiota in cancer pathogenesis and immunity: from mechanisms of action to therapeutic opportunities

“…The fungal species including Metarhizium acridum CQMa 102, Phaffia rhodozyma and S. cerevisiae YJM1338 were enriched in tumor tissues of patients with papillary thyroid carcinoma (PTC) (61). Three PTC subtypes, Classical (CPTC), Follicular Variant (FVPTC) and Tall Cell (TCPTC), showed a similar microbial composition and richness.…”