Abstract B92: Metabolomic landscape of African American prostate cancer: Insights into the biologic basis of the racial disparity

Abstract

Abstract African American (AA) men have an approximately 60% higher incidence of prostate cancer (PCa) and have about two times greater risk of dying of the disease than their European American (EA) counterparts. Despite this staggeringly unequal burden of PCa incidence and outcome between AA and EA men, there is limited insight into the molecular mechanisms associated with this racial disparity. Using state-of-the-art mass spectrometry platform, we uncovered the very first metabolic and lipidomics landscape in PCa/benign adjacent tissue pairs and paired plasma and urine containing epidemiologic meta-data from ancestry-typed AA and EA men. A total of 190 polar and mid-polar metabolites and 495 lipids were measured in tissues and 183 metabolites and lipids were examined in the plasma and urine samples. AA PCa tissue and plasma signatures had unique alterations in metabolites and key enzymes associated with the methionine-homocysteine pathway, including adenosine and inosine levels, compared to corresponding tissues and plasma from EA case controls and EA PCa tissues. Intriguingly, methionine levels in AA PCa were also portrayed by distinct dietary practices in these patients. In addition, AA PCa tissues demonstrated unique patterns of bioenergetic metabolites and accumulated lipids reflecting impaired mitochondrial activity and TCA cycle. Further characterization of these first-in-the-field findings demonstrating reprogrammed metabolism in AA PCa relative to EA tumors could reveal insights into the biologic basis of PCa disparities and novel areas for therapeutic intervention. Citation Format: Stacy M. Lloyd*, Jie H. Gohlke*, Sumanta Basu*, Vasanta Putluri,Shaiju K Vareed, Rebeca San Martin, Thekkelnaycke Rajendiran, Tiffany A. Dorsey, Bandana Prasad, Rajni Sonavane, Uttam Rasaily, James Henderson, Balasubramanyam Karanam, Harene Venghatakrishnan, Salil Bhowmik, Alexander Zaslavsky,Nilanjan Guha, Rick Kittles, Stefan Ambs, Michael Ittmann,David Rowley, Ganesh Palapattu, Nagireddy Putluri,George Michailidis, Arun Sreekumar. Metabolomic landscape of African American prostate cancer: Insights into the biologic basis of the racial disparity [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B92.