Differences in the prostate tumor transcriptome by genetic ancestry

(A) Heatmap of expression of 220 genes differentially expressed between genetic ancestry groups with fold-change >2. Red denotes a gene more highly expressed in AA men, and blue more highly expressed in EA men. Genetic ancestry is shown using EIGENSTRAT classification (top) and STRUCTURE-estimated composition (bottom). (B) Circle plots showing (from inner to outer): 1) distribution of types of differentially expressed genes (DEGs); 2) fold-change in gene expression comparing AA to EA men in tumor tissue; 3) fold-change in gene expression comparing AA to EA men in tumor-adjacent normal tissue; 4) fold-change in gene expression comparing tumor to tumor-adjacent normal tissue; 5) fold-change in gene expression comparing AA to EA men for protein-coding genes evaluated in Wallace et al microarray dataset. (C) Enrichment in DEGs for genes regulated by eQTLs in normal prostate tissues (eGenes) and genes identified in prior GWAS of TWAS of CaP risk. The proportion of eGenes was higher among the DEGs than non-DEGs and increased with more stringent cutoffs in the FDR (upper plot). The prevalence odds of eGenes were higher among the DEGs, while the prevalence odds of GWAS and TWAS genes did not differ between DEGs and non-DEGs (lower plot). (D) Gene sets identified through gene set enrichment analysis that were significantly activated (upper plot; n=18) and repressed (lower plot; n=13) in tumors of AA men (FDR corrected p less than 0.1 through permutation test). Candidate gene sets were identified from the BioCarta pathway database and Wallace et al. Many gene sets pertaining to immune-related signaling were activated in AA tumors, while sets related to PTEN/PI3K were repressed in AA tumors. (E) Network plot of the 18 gene sets significantly activated in AA tumors. Nodes are grouped by gene set function. Node size is proportional to the number of genes in the gene set and node shading reflects the Normalized Enrichment Score (NES). An edge indicates there are shared genes between gene sets and edge shading reflects the number of shared genes. (F) Enrichment plots of the Wallace Prostate Cancer Race (Up), T Cytotoxic Cell Surface Molecules, Wallace Prostate Cancer Race (Down), and PTEN dependent cell cycle and apoptosis gene sets.