Abstract B37: Differential mRNA expression, microRNA regulation and gene networks are associated with the prostate cancer disparities in African American and Caucasian American populations

Abstract

Abstract Prostate cancer (PCa) is a disease conferred by multiple gene mutations, numerous alternations in gene expression and aberrant changes in genome composition/architecture. An area of research that continues to garner attention is PCa health disparities, wherein the African American (AA) population exhibits higher incidence and mortality rates compared to Caucasian Americans (CA). Although accumulating evidences have suggested that the widespread microRNA deregulation may play crucial role in cancer development, the relationship between population-specific microRNAs and PCa disparities remains largely unknown. To identify the genetic predispositions and oncogenic networks associated with the observed PCa disparities, we applied a systems biology approach by combining mRNA expression profiling, microRNA profiling and microRNA target searches to characterize the genetic portraits of PCa in AA and CA populations. Affymetrix human exon 1.0ST arrays and Agilent human miRNA V2 arrays were used to analyze the global mRNA and microRNA expression profiles in AA and CA prostate tissue samples. From the mRNA profiling results, a 4-way statistical analysis (t-test with 10% FDR; AA normal vs. CA normal, AA cancer vs. CA cancer, AA cancer vs. AA normal, and CA cancer vs. CA normal) has identified 275 to 987 genes with differential expression in the 4-way comparisons. Furthermore, pathway analysis revealed that the mis-regulated testosterone metabolic pathway, activated inflammatory response and up-regulated oncogenic pathways (ERK, JNK and p38) are associated with the biological differences when comparing AA normal to CA normal, AA cancer to CA cancer and AA cancer to AA normal. In addition, a microRNA/mRNA-regulated network, generated by integrating microRAN-targeted mRNAs and mRNA profiling data, suggested that the population-specific microRNAs may contribute to differential cell-cycle control, protein synthesis and cell apoptosis in AA and CA prostate cancers. Our study has demonstrated that differential gene-network regulation, driven by the population-specific mRNA and microRNA expression, may explain in part the biological differences between AA and CA prostate cancers. This work was supported by NCI grant 5U01-CA-116937 and ACS-IRG-08-091-01. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B37.