Institution: Ponce Medical School Foundation Inc

Email: cjdiaz@psm.edu

Prostate cancer (PCa) is the leading cause of cancer-related death in Puerto Rican men. The incidence and mortality rates of PCa in the Puerto Rican population are higher than in any other Hispanic/Latino group in the United States. In addition to socioeconomic contributors to these health disparities, differences in molecular features in prostate tumors indicate that tumor biology may also contribute to disparate outcomes of certain men with PCa. The paucity of studies involving Puerto Rican men significantly hinders evidence-based improvements in care for these patients. In particular, current risk assessment following diagnosis involves the consideration of variables including age, serum prostate specific antigen, and extent of disease present at biopsy. However, these universal parameters do little to account for heterogeneity among ethnic populations. The lack of validated indicators of aggressive disease constitutes a gap in knowledge that translates to observably disparate cancer outcomes. This proposal aims to address this urgent need for clinically relevant biomarkers to facilitate risk stratification for PCa patients in the Puerto Rican population. Building on growing evidence supporting the role of lipid metabolism and altered immune regulation in tumorigenesis and disease progression, the objective of this study is to define key pathways at the interface of immunometabolomics functioning within aggressive PCa in Puerto Rican men. The proposed work is designed to maximize the yield from valuable banked prostate tumor tissues from Puerto Rican men, employing technological advancements including untargeted global metabolomics and lipidomics analyses, high-dimension immune phenotyping, and precision medicine-based evaluation of novel genomic signatures. The long-term goal of this study is to identify and target central mechanisms driving aggressive PCa in Puerto Rican men. Its central hypothesis is that immunometabolomic assessment of prostate tumor microenvironment holds prognostic significance for Puerto Rican men with PCa. The following specific aims will be pursued: (1) Identify intratumoral lipid metabolites associated with aggressive PCa in Puerto Rican men, and (2) Evaluate immune content analysis and high-dimension phenotyping of tumor-infiltrating immune cells as biomarkers of aggressive PCa in Puerto Rican men. As the first of its kind to integrate a multi-omics approach to identify biomarkers to improve risk stratification for Puerto Rican men with PCa, the impact of its findings is expected to contribute to improved understanding of tumor biology and the utility of precision medicine tools and future targeted or immunotherapies in patients with PCa in Puerto Rico.