Abstract 6096: Bladder cancer microbiome and its association with chemoresponse

Abstract

Abstract Background: The microbiome is widely known to cause cancer, modify its behavior, and alter the way therapies interact with tumors. Despite the urinary microbiome being one of the most clinically significant microbiomes in human health, is one of the least well-described. Results: To begin to annotate the urinary microbiome present in bladder cancers, we analyzed raw sequencing data from the Cancer Genome Atlas (TCGA) from 116 tumors (duplicates from 22 tumors), 22 adjacent normal bladder tissues, and 99 blood samples to identify reads originating from known microbiota. Twenty-seven viral and bacterial species were found to be enriched in the tumor samples. Bacterial species such as B. thetaiotamicron, A. mucinaphila and Bifidobacterium spp. with known positive association with immune checkpoint blockade therapy against CTLA-4 and PD-L1 were frequently found in these tumor samples. We also found sex-specific enrichment of genera such as Lactobacillus and Prevotella in female bladder cancer patients which also are prevalent in the normal female genitourinary tract. A. prevotii and F. magna were also enriched in females. We also found a correlation between Prevotella and TCGA subtypes III and IV (basal expression subtypes), suggesting a link between enrichment of certain microbial species and bladder cancer subtypes. Finally, single sample gene set enrichment analysis using the Hallmark and KEGG gene sets revealed the association of Mycoplasma with the Hallmark DNA repair gene set and with the KEGG pyrimidine metabolism pathway that can be further studied to ascertain its effects on DNA damaging chemotherapeutic agents. To corroborate these findings, we performed 16S metagenomics from urine pellets of 40 bladder cancer patients undergoing radical cystectomy on a prospective clinical trial (NCT02968732). We found one predominant genus consistent with prior urinary metagenomics studies in samples from most of the patients. Thirty eight of the 58 genera identified in the TCGA analyses were also present in these urine samples. Further correlation with response to clinical metadata is ongoing. Conclusions: Description of the bladder cancer microbiome is the first step in approaches to manipulate it for therapeutic gain. Citation Format: Rashida Ginwala, Erika Nachman, Suraj Peri, Jodie Franklin, Leigh Greathouse, Molly Ingersoll, Alexander Kutikov, James R. White, Philip H. Abbosh. Bladder cancer microbiome and its association with chemoresponse [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6096.