Our research aimed to uncover the biological differences that contribute to these disparities, as we believe that understanding these differences is crucial for developing effective treatment strategies that address the unique needs of Black men with prostate cancer. By analyzing large-scale transcriptome and epigenome data, we were able to gain insights into the molecular mechanisms that drive these disparities and identify potential therapeutic targets. By doing so, we can move closer to reducing the persistent racial disparities in prostate cancer outcomes and improving the health outcomes of Black men with this disease.
Through a comprehensive transcriptomic analysis of prostate cancer from 305 Black and 238 White men, we identified distinct biological differences between the two racial groups. At the gene level, we found that Black men had higher levels of differentially expressed genes compared to White men. Functional analysis revealed that MYC-related pathways were activated in White men, while inflammation, steroid hormone response, and cancer progression-related pathways were activated in Black men. We also found that Black men had higher levels of immune cells, such as T cells, macrophages, and dendritic cells, in their tumors.
One of the most striking findings was the consistent activity of 10 transcription factors in Black men across all three cohorts, even when patients were stratified by Gleason sum. This suggests that Black and White men use different transcriptional programs, even within the same grade of patients. To understand the transcriptional network that differentiates Black and White men, we reconstructed a network model using the 10 transcription factors overactive in Black men compared to White men (Figure 1).
This illustrates the highly wired and consistently active transcriptional programs by the 10 transcription factors in Black prostate cancer. We then used genome-wide chromatin binding profiles to confirm that the androgen receptor (AR) centered transcription factor network plays a significant role in the differences in transcriptional programs between Black and White men. Higher AR binding signals were found in Black men for 10 key transcription factors and their target genes, suggesting that the differential transcriptional programs are real and may be largely regulated by the AR.
These findings have significant implications for the development of tailored therapeutic strategies and improving outcomes for Black men with prostate cancer. The transcriptional and epigenomic differences between races suggest that tumors may respond differently to certain therapies, particularly immunotherapies, by race. We believe that understanding these biological differences is crucial for developing effective treatment strategies that address the unique needs of Black men with prostate cancer. Further research is needed to fully understand the mechanisms driving these differences and to develop targeted therapies that address the unique needs of Black men with prostate cancer.
Written by: Minhyung, PhD & Sungyong You, PhD, Cedar-Sinai Medical Center, Los Angeles, California.
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