The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response
Abstract
African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and increased lipid levels in AA prostate cancer. In a metastatic prostate cancer cohort, upregulated lipid metabolism associated with poor prognosis. These findings offer the first insights into ancestry-specific differences in the prostate cancer AR cistrome. The data suggest a model whereby increased androgen signaling may contribute to higher levels of lipid metabolism, immune response, and cytokine signaling in AA prostate tumors. Given the association of upregulated lipogenesis with prostate cancer progression, our study provides a plausible biological explanation for the higher incidence and aggressiveness of prostate cancer observed in AA men.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 22, 2022
- Source ID
- 10.1158/0008-5472.can-21-3552
Entities
People
- Amit K Dash
- Christel M Davis
- Collin Mccoll
- Connor Bell
- Cristian Coarfa
- Dallin Lowder
- Darlene G. Skapura
- Elio Adib
- Elisa Benedetti
- Erik A Ehli
- Gitanjali Lakshminarayanan
- Heather M. McClure
- Jacob E Berchuck
- Jenny Deng
- Ji-Heui Seo
- Jin Na Shin
- Kaitlin M. Kelleher
- Kinza Rizwan
- Mark M. Pomerantz
- Massimo Loda
- Matthew L Freedman
- Matthew P. Davidsohn
- Matthew Robertson
- Michael M. Ittmann
- Nicholas Mitsiades
- Patricia D Castro
- Ryan Carelli
- Salma Kaochar
- Sandra L. Grimm
- Sarah Abou Alaiwi
- Sylvan C. Baca
- Talal El Zarif
Organizations
- Baylor College of Medicine
- Brigham and Women's Hospital
- Dana–Farber Cancer Institute
- National Cancer Institute
- National Institutes of Health
- United States Department of Defense
- Weill Cornell Medicine