MP66-04 CABAZITAXEL INHIBITS THE PROLIFERATION OF HUMAN CASTRATION-REFRACTORY PROSTATE CANCER CELLS IN VITRO AND ENHANCES THE ANTI-TUMOR PROPERTIES OF THE ANGIO-INHIBITORY PIGMENT EPITHELIUM-DERIVED FACTOR IN VIVO WITH A GREATER EFFICACY THAN DOCETAXEL

therapeutic response. The goal of this study was to evaluate and genetically characterize exosome derived RNA (exoRNA) isolated from blood of metastatic CRPC patients. METHODS: Whole blood samples from 18 consented clinically annotated mCRPC patients and 1 normal control were collected. Exosomes were isolated with ultracentrifugation and exoRNA extracted. Following library prep, paired-end sequencing was performed using Illumina Hi-Seq 2000. A bioinformatics pipeline was used for data prepossessing including alignment, duplicate removal, normalization and variant calling. Visualization and differential analyses were performed with SNP & Variation Suite v8.x. RESULTS: In exoRNA there is evidence of extensive chromosomal rearrangement resulting in a myriad of gene fusions and isoforms. Through preliminary analyses we identified 39 genes commonly expressed in the exosomes of these mCRPC patients. These include PDPK1, USP9X, MAGI2, HMGA2 and PTGFR all of which have been previously expressed in prostate cancer tissue. A diverse variety of lcnRNA, ncRNA and miRNA were also identified in circulating exosomes. Validation of these alterations and additional analyses evaluating translocations and splice variants, PCR validation, and/or direct tumor based nucleic acid assays is ongoing. CONCLUSIONS: These preliminary analyses of circulating exoRNA have identified gene expression signatures of several prostate cancer associated transcripts. Ultimately, the identification of PCa associated transcripts in plasma derived exosomes provides evidence that exosomes and exosomal cargo may serve as biomarker in CRPC patients. Exosomes and exoRNA may provide otherwise unattainable insight into tumor evolution and disease progression. Additional studies evaluating the clinical relevance and prognostic value of exosomal RNA will be critical for biomarker development.