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.
Highlights
Racial disparities in prostate cancer have not been well characterized on a genomic level
This small size of American men (AAM) samples has led to underpowered studies to identify the meaningful biological difference and is not enough to capture the heterogeneity in AAM populations
This study investigates biological differences between AAM and European-American men (EAM) is a large transcriptomic cohort with more than 50% being AAM
Summary
Racial disparities in prostate cancer have not been well characterized on a genomic level. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. Significant racial disparities exist in PCa outcomes, with African-American men (AAM) experiencing a higher incidence (186.8 vs 107.0 per 100,000) and mortality rate (40.8 vs 18.2 per 100,000) than European-American men (EAM)[1]. Previous studies have shown that multiple factors including, cultural, socioeconomic, psychosocial, and healthcare access disproportionately influence higher cancer burden and poor disease outcomes in AAM2,3, our knowledge of the extent to which tumor biology contributes to the reported level of disparities is limited. To unravel race-specific unique molecular pathways implicated in PCa, we leveraged a multi-institutional database and analyzed genomic differences between AAM and EAM
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