RNA expression differences in prostate tumors and tumor-adjacent stroma between Black and White Americans
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Farah Rahmatpanah1, Gabriela De Robles1, Michael Lilly2, Thomas Keane3, Vinay Kumar1, Dan Mercola1, Pavneet Randhawa1 and Michael McClelland1,4
1 Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA
2 Department of Hematology and Oncology, Medical University of South Carolina, Charleston, SC 29425, USA
3 Department of Urology, Medical University of South Carolina, Charleston, SC 29425, USA
4 Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697, USA
|Farah Rahmatpanah,||email:||[email protected]|
|Michael McClelland,||email:||[email protected]|
Keywords: prostate cancer; tumor-adjacent stroma; African ancestry; European ancestry; RNA-seq analysis
Received: May 20, 2021 Accepted: June 22, 2021 Published: July 20, 2021
Prostate cancer (PCa) in Black Americans (BA) is diagnosed at an earlier median age and a more advanced stage than PCa in White Americans (WA). Tumor-adjacent stroma (TAS) plays a critical role in tumorigenesis of prostate cancer. We examined RNA expression in both tumor and TAS of BA compared to WA. After evaluating the geographical ancestry of each sample, preliminary analysis of our own RNA-seq data of 7 BA and 7 WA TAS revealed 1706 downregulated and 1844 upregulated genes in BA relative to WA PCa patients (padj < 0.05). An assessment of published RNA-seq data of clinically matched tumor-enriched tissues from 15 BA and 30 WA patients revealed 932 upregulated and 476 downregulated genes in BA relative to WA (padj < 0.05). When TAS and tumor epithelial cohorts were compared for the top 2500 statistically significant genes, immune responses were downregulated in BA vs WA TAS, while T cell-exhaustion pathways and the immune checkpoint gene CTLA4 were upregulated in BA vs WA tumors. We found fewer activated dendritic cells in tumor and more CD8 T-cells in TAS of BA versus WA PCa patients. Further characterization of these differences in the immune response of PCa patients of distinct geographical ancestry could help to improve diagnostics, prognostics, and therapy.
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