Abstract
Despite reported influences of the intratumoral microbiome on cancer progression, its role in this subtype remains unclear. This study aimed to characterize the microbial landscape and signatures of kidney renal clear cell carcinoma using RNA-Seq data from The Cancer Genome Atlas. Following microbial decontamination, differential microbial analysis was conducted between tumorous and adjacent non-tumorous samples. Compared to non-tumorous samples, tumorous microbiota exhibited reduced α and β diversity and distinct phylum-level communities. Differential microbial analysis between patients exhibiting long and short overall survival revealed ten significant differential microbial genera, with six genera correlating with a positive prognosis (Plasmodium, Babesia, Toxoplasma, Cytobacillus, Alicyclobacillus, Verrucomicrobium) and four with a negative prognosis (Colletotrichum, Leuconostoc, Gluconobacter, and Parabacteroides). Employing Cox regression analysis and support vector machines, a prognosis-related microbiome risk signature was developed, achieving an AUC of 0.809. Based on this risk signature, two microbiome-based subtypes were found to be significantly associated with distinct clinical prognoses and immune microenvironments. These findings were corroborated by significant correlations between prognostic-relevant microorganisms and 30 immune-related differentially expressed genes. Specifically, microbial genera associated with a negative prognosis were linked to a pro-tumor acute inflammatory immune response, whereas genera related to a positive prognosis were associated with an anti-tumor adaptive immune response. In conclusion, microbiome-based subtyping revealed correlations between tumor microbiome, clinical prognosis, and tumor microenvironment, indicating intratumoral microbiota as a promising prognostic biomarker for kidney renal clear cell carcinoma.