Abstract 3771: Mitochondrial metabolism and racial disparity of bladder cancer

Abstract Potential differences and mechanism in metabolism among bladder cancer (BLCA) patients of diverse race or ethnicities remain largely unexplored. Even though the incidence rate of BLCA in African Americans (AA) is nearly half as that of European Americans (EA), but AA have the worst survival. We performed the transcriptomics and metabolomics profiling in ancestry verified patients from AA and EA BLCA and observed mitochondrial complex activities were uniquely enriched in AA tumors compared to EA tumors. In addition, in vitro assay demonstrated differences in mitochondrial complex protein and activity between AA and EA BLCA. We further confirmed the reprogramming of mitochondrial metabolism using in vitro 13C labeled tracers in both AA and EA BLCA. Integration of metabolomics and transcriptomics data reveals the enrichment of mTOR pathway in AA BLCA. Our findings indicate that an elevated mitochondrial oxphos activity through mTOR activation could be a factor for AA BLCA progression and provide the rationale to examine mitochondrial specific inhibitors along with mTOR inhibitors to target BLCA on subset of patients from the AA community. Citation Format: Karthik Reddy Kami Reddy, Jun Hyoung Park, Roni J. Bollag, Allison Bellman, Martha Terris, Seth P. Lerner, Leomar Y. Ballester, Yair Lotan, Benny Abraham Kaipparettu, Nagireddy Putluri. Mitochondrial metabolism and racial disparity of bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3771.