Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy.
Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.
Communications biology. 2021 Jun 03*** epublish ***
Walter Rayford, Alp Tuna Beksac, Jordan Alger, Mohammed Alshalalfa, Mohsen Ahmed, Irtaza Khan, Ugo G Falagario, Yang Liu, Elai Davicioni, Daniel E Spratt, Edward M Schaeffer, Felix Y Feng, Brandon Mahal, Paul L Nguyen, Robert B Den, Mark D Greenberger, Randy Bradley, Justin M Watson, Matthew Beamer, Lambros Stamatakis, Darrell J Carmen, Shivanshu Awasthi, Jonathan Hwang, Rachel Weil, Harri Merisaari, Nihal Mohamed, Leslie A Deane, Dimple Chakravarty, Kamlesh K Yadav, Kosj Yamoah, Sujit S Nair, Ashutosh K Tewari
The Urology Group LLC, Memphis, TN, USA., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Urology, Medstar Georgetown University Hospital, Washington, DC, USA., Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA., Decipher Biosciences, San Diego, CA, USA., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA., Department of Urology, Northwestern University, Chicago, IL, USA., Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, USA., Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA., Haslam College of Business, University of Tennessee, Knoxville, TN, USA., WellStar Urology, Marietta, GA, USA., Georgia Urology, Atlanta, GA, USA., Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA., Department of Clinical Medicine, University of Turku, Turku, Finland., Department of Urology, Rush University Medical Center, Chicago, IL, USA., Sema4, a Mount Sinai venture, Stamford, CT, USA., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .