Epigenetic Changes and Clinicopathological Characterization of Prostate Cancer from Patients of African Ancestry
Abstract
Prostate cancer health disparity has been attributed to ethnicity-related differences. In particular, men of African ancestry have a higher risk of prostate cancer and more aggressive tumor progression than men of European ancestry. However, the factors and underlying mechanisms that lead to those ethnicity-related disparities are not yet fully understood. Epigenetics, the study of modifications that do not change the DNA sequence but can affect gene activity, enables us to unravel the hidden molecular mechanisms of gene regulation that give rise to prostate cancer. In Aim 1, we will identify epigenetic changes linked to aggressive prostate tumors from men of African ancestry. First, we will generate genome-wide epigenome datasets of matched metastatic and primary prostate tumors from men of African ancestry. Next, we will identify and characterize epigenetic changes linked to metastatic prostate tumors from men of African ancestry by performing cutting-edge bioinformatic and statistical analyses. To characterize the changes leading to prostate cancer, we have collaborated in profiling the genomes of prostate tumor tissues and categorized the tumor tissues to the eight prostate tumor molecular subtypes. However, the way each subtype influences aggressive tumor behavior is not well understood. In Aim 2, we will identify key epigenetic alterations associated with aggressive prostate tumor molecular subtypes by integrating genomic, epigenomic, and gene expression datasets. This research proposal aims to address several FY20 Prostate Cancer Research Program Overarching Challenges. First, we propose to generate and analyze genome-wide epigenome datasets of prostate tumors from men of African ancestry to reduce lethal prostate cancer in people of African descent, Veterans, and high-risk and underserved populations. Until now, a majority of prostate cancer epigenome datasets had been generated from patients of European ancestry; additional epigenome datasets from prostate cancer patients of African ancestry are greatly needed. Second, our newly generated datasets and cutting-edge analyses focusing on metastatic and aggressive prostate tumors will help define the biology of lethal prostate cancer in order to reduce prostate cancer-related death. Ultimately, novel findings and newly uncovered biology of aggressive prostate cancer from the proposed study will facilitate the development of treatments that improve the outcomes of men with lethal prostate cancer. In summary, the proposed study will uncover new epigenetic changes that alter gene activity in aggressive prostate tumors. Key epigenetic and gene activity changes identified in this study will be potential biomarkers and candidate therapeutic targets for the diagnosis and treatment of metastatic prostate tumors from men of African ancestry and aggressive prostate tumor molecular subtypes. Successful completion of the proposed study will accelerate the development of improved targeted diagnostic and therapeutic tools for aggressive prostate tumors in the field. The ability to provide more accurate diagnoses and targeted treatments will benefit patients with aggressive forms of prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110805
Entities
People
- Suhn K Rhie
Organizations
- United States Army
- University of Southern California