It has known that bladder cancer (BCa) mortality is higher in African American patients. Disparity exists between African-American (AA) and European-American (EA), in the clinical outcome of BCa. The long-term objective of our research plan is to reduce the disproportionate effects of bladder cancer (BCa) on African American. A guiding principle of our methodology is that alterations in mitochondrial metabolites exist between African American and European American BCa and that these differences can explain, in part, BCa health disparity. In this application, we propose to use the technique of metabolomic profiling to uncover these underlying differences. To date, a metabolomic analyses aimed at understanding of bladder cancer health disparity has not been reported. We have recently published the first study describing metabolic alterations associated with bladder cancer. In preliminary studies, we have profiled the metabolome of BCa from AA and EA patients and identified a distinct AA race-specific expression pattern in mitochondrial metabolites and lipids. In this proposal, we will i) characterize the mitochondrial associated metabolites in AA and EA BCa, ii) verify the D-2HG and associated enzymes (GLS, ADHFE1, and IDH1/2) in BCa patients and establish a therapeutically targeted deregulation pathway for glutamine metabolism in AA BCa iii) assess the levels of lyso PC and PC and the function of their metabolizing enzymes PLA1A and LRAT in AA BCa. The successful completion of the proposed studies will have a significant impact in the field of Bladder cancer health disparity and metabolism. Importantly, findings from our study have the potential to reveal racially exclusive metabolic markers and therapeutic targets for BCa. Taken together, the information gleaned from this proposal could rapidly revolutionize current diagnostic, prognostic and therapeutic approaches by revealing the biological underpinnings of bladder cancer health disparity.
This proposal expects to develop a panel of mitochondrial metabolic markers in tissues and urine. The study is supported by a seminal publication highlighting the ability of the PI to develop urine-based metabolic markers for bladder cancer smoker by: 1. utilizing urine based metabolites as non-invasive biomarkers; and, 2. developing race associated perturbed metabolic pathways specific to bladder cancer that could be further harnessed to develop better treatment strategies or combinatorial therapy with the existing drugs. Overall, this proposal is expected to delineate 2-Hydroxy glutaric acid, glutamine metabolism, and associated mitocondrial metabolites with AA BCa and develop a first-generation panel of metabolic markers in urine of AA BCa patients.
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