Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.

Abstract

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.

• Authors: 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
• Journal: Communications biology (Commun Biol) Vol. 4 Issue 1 Pg. 670 (06 03 2021) ISSN: 2399-3642 [Electronic] England
• PMID: 34083737 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Topics

• Black or African American (genetics, statistics & numerical data)
• Aged
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Genomics (methods)
• Health Status Disparities
• Humans
• Immune System (immunology, metabolism)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Prostatic Neoplasms (ethnology, genetics, immunology)
• Retrospective Studies
• United States
• White People (genetics, statistics & numerical data)