(UroToday.com) The 2025 SESAUA annual meeting featured a prostate cancer session and a presentation by Matthew Cole discussing gene expression differences and pathway activation by race in ERG positive prostate cancers. Prostate cancer incidence and mortality are higher in African-American men compared to White men, driven by social determinants and molecular differences.
ERG positivity, an early molecular alteration in prostate cancer development, exhibits differing prevalence between African American and White patients. Nevertheless, the extent of race-based variations within the tumor subtype and their potential clinical impact remain largely unexplored. This study presented at SESAUA 2025 investigated differential gene expression and biological pathways in ERG positive prostate cancer across a racially diverse cohort.
This study used the publicly available GSE169038 dataset, analyzing whole-transcriptome profiles (22,236 transcripts) from 1,152 men with clinically significant prostate cancer (Grade Group ≥ 2) who underwent radical prostatectomy. ERG positive or ERG negative status was determined via Gaussian Mixture Modeling. Differential gene expression was identified using the linear models for microarray data (Limma) package, with a false discovery rate of 5%. Gene Set Enrichment Analysis was conducted using EnrichR with a false discovery rate threshold of 10%, corrected for multiple comparisons by the Benjamini-Hochberg method.
The cohort included 556 White men and 596 African American men with the following baseline characteristics:
ERG positivity was more prevalent in White (40%, n = 209) than African American (23%, n = 127) patients (p < 0.001):
Among 5,814 differentially expressed genes in ERG positive tumors, 2,605 (45%) were shared between both groups. However, 1,987 (34%) were unique to White patients and 1,312 (23%) to African American patients. Shared pathways involved androgen and estrogen response, fatty acid metabolism, and apoptosis (p < 0.05). White-specific genes were linked to the p53 pathway (p = 0.003), while African American-specific genes were associated with E2F target pathway (p = 0.008). Limitations of the current analysis include the results being mostly descriptive and do not link observed differences to clinical outcomes. Additionally, the RNA expression data were derived from Decipher testing based on clinical indications, thus, this study represents a higher risk cohort than the standard radical prostatectomy population.
Matthew Cole concluded his presentation discussing gene expression differences and pathway activation by race in ERG+ prostate cancers with the following take-home points:
- This study validated previously observed differences in ERG prevalence between African American and White patients with clinically significant (Grade Group ≥ 2) prostate cancer
- Further, this analysis identified distinct genetic signatures between African American and White patients within the ERG+ prostate cancer molecular subtype.
- Future studies should investigate the biological mechanisms underlying the distinct genetic profiles observed. Understanding how race-based molecular differences contribute to prostate cancer progression could decrease race based disparities in treatment.
Presented by: Matthew Cole, Department of Urology, Vanderbilt University Medical Center, Nashville, TN
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Southeastern Section of the American Urological Association (SESAUA) 2025 Annual Meeting, Nashville, TN, Wed, Mar 12 – Sat, Mar 15, 2025.