INTRODUCTION AND OBJECTIVES: Kidney cancer is a unique tumor with the ability to propagate tumor into the vascular system termed venous tumor thrombus (VTT). New evidence suggests there may be interactions between resident tissue microbes and cancer behavior. We investigate the microbiome of renal cell carcinoma patients with VTT. METHODS: Fresh radical nephrectomy specimens were obtained from the operating room and include normal adjacent, tumor, and tumor thrombus. Raw paired-end RNA-seq reads were first filtered for quality, Illumina adaptor sequences, and minimum length (95bp) using Trimmomatic. Bowtie 2 searches of the NCBI RefSeq database were performed including fungal, eurkaryotic, bacterial, archaeal and viral members. Pathoscope was extended to include total genome coverage estimates for taxonomic assignment. After assessment of total genome-specific coverage by mapped reads, those microbial members with less than 0.1% average genome coverage were removed from consideration. The paired t-test and paired Mann-Whitney U test were employed to evaluate the statistical significance of differences in taxonomic percentage abundance between groups of interest. RESULTS: We identified fairly minimal numbers of bacteria with most samples having a proportionally high level of Cutibacterium (proprionobactirum) acnes (Figure1). However, there is remarkably more bacterial diversity within the primary tumor specimens that there is in normal adjacent tissue or the VTT. Micrococcus luteus most demonstrates the expansion into the tumor from adjacent normal then nearly disappears in the tumor thrombus (adj. p=0.059). Another finding is that in 50% (3/6) patients we identified bacteria resident to the oral microbiome that were nearly exclusively found in the primary tumor specimen. CONCLUSIONS: Microbiome diversity is found with the primary kidney cancer site and is lost in tumor thrombus propagation. We hypothesize that changes in the tumor microenvironment are related to alterations in tumor-associated bacteria. Potential migration of resident oral microbiome to the kidney may be linked to kidney cancer outcomes and should the further explored. [Figure: see text] Source of Funding: Roger L. and Laura D. Zeller Charitable Foundation.
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