Project 1

Substantial human variation in prostate cancer (PCa) incidence and mortality have been observed. For example, PCa incidence is 1.5 times higher in African American (AA) men than in non-Latino White (WH) men, and AA men are 2.5 times more likely to die from the disease. The biological determinants underlying this difference remain poorly understood. Our prior work and studies by others have shown that somatic genomic alterations, transcriptomic signatures, and immune tumor microenvironment (TME) components differ significantly between populations that have higher PCa mortality rates, suggesting that the molecular features associated with aggressive disease may also differ by genetic ancestry. Despite progress, further advances in prognostic biomarkers require more well-annotated cohorts of high-risk men. In this collaborative project between Johns Hopkins University (JHU) and Howard University (HU), we will conduct genomic and epigenomic profiling of metastatic PCa to identify biomarkers of lethal disease. We will evaluate novel and established in situ biomarker assays that reflect tumor genomic and TME features in relation to clinical outcomes and genetic ancestry. Aims of the project are: Aim 1: Establish a unique cohort of locally metastatic prostate cancer from high-risk men for genomic and epigenomic profiling to assess molecular differences between primary and metastatic disease. Aim 2: Perform genomic and epigenomic profiling of distant metastatic disease in this sample to identify biomarkers associated with lethal PCa. Aim 3: Validate in situ molecular biomarkers of tumor progression using the combined JHU-HU PCa tissue cohorts. This project aims to define biomarkers of aggressive prostate cancer that can improve prognostic accuracy and inform precision medicine strategies for populations at high risk for aggressive disease and PCa mortality.