MP56-10: Characterization and functional analysis of microbiome in bladder cancer.

Laura Bukavina*, Philadelphia, PA, Adam Calaway, Ilaha Isali, Megan Prunty, Cleveland, OH, Mohit Sindhani, Delhi, India, Mahmoud Ghannoum, Mauricio Retuerto, Gregory MacLennan, Sarah Markt, Lee Ponsky, Cleveland, OH, Philip Abbosh, Philadelphia, PA

Introduction: The role of microbiome in genitourinary cancer is an emerging field, with evidence implicating the important role of microbiome as causative factors or cofactors in tumorigenesis and drug metabolism. Our study aims to characterize healthy and bladder cancer enterotypes in the gut and identify functional alterations through the use of metagenomics data.

Methods: After prospective collection of 29 rectal swab samples of bladder cancer (BCa) patients undergoing cystectomy, and 32 healthy volunteers, we perform 16S rRNA amplicon sequencing on 61 samples (29 with bladder cancer, 32 without cancer). The a- and b-diversity analyses were performed using QIIME. The MannWhitney U test was employed to evaluate the statistical significance of b-diversity distances within and between groups of interest.

Results: The microbial diversity differences between Bca and normal samples showed no differences across alpha diversity metrics (Shannon diversity p > 0.05), however, there was significant difference in clustering of organisms as determined by principal coordinate analysis ( PCoA) ordination (p = 0.002). Furthermore, upon stratification of patients on smoking status (all healthy = nonsmokers), clustering persisted, albeit non smokers with bladder cancer displayed an intermediate across PCoA. Bca samples exhibited higher LDA score Campylobacterales (log change 8.0, p < 0.001, p < 0.001) ,Fusobacteriales (log change 6.11, p < 0.001/ p < 0.01), Epysipelotrichales (log 2.55, p < 0.001/p < 0.001), Actinomycetales (log change 1.86, p = 0.001/ p < 0.001), Verrucomicrobiales (log change 1.78, p = 0.017/p = 0.031) and Enterobacteriales (log change -1.54,p = 0.017/ p = 0.132).

Conclusions: In conclusion, our study provides preliminary evidence that the GI microbiota is different in bladder cancer patients. Collectively, our study highlights distinct microbial overexpression of Campylobacter and Fusobacterium in Bca cohort not previously reported, both implicated in tumorigenesis, and could serve as a target that could be modulated to enhance treatment response.

Source of Funding: P30CA043703