Potential of miRNAs in Plasma Extracellular Vesicle for the Stratification of Prostate Cancer in a South African Population

SIMPLE SUMMARY: Prostate cancer (PCa) is the most lethal cancer among African men. Extracellular vesicles (EVs), including exosomes, are released from cancer cells as a form of intercellular communication that can promote cancer growth, increasing invasion and metastasis. EVs are nano-sized vesicles that contain cargo such as microRNA (miRNA), mRNA, and proteins. miRNAs are non-coding RNA that regulate gene expression and are partly responsible for the cancer-promoting function of EVs. As PCa is more aggressive in African populations, it is vital to know which miRNAs are within the EVs of these patients. In this study, we identify and quantify the EV miRNAs in blood plasma from South African patients with low and high Gleason score PCa (an indication of cancer’s aggressive nature). In addition, we use quantitative PCR to evaluate the EV miRNA levels in benign prostatic hyperplasia (BPH) compared to PCa to identify putative biomarkers for the South African population. ABSTRACT: Prostate cancer (PCa) is the most common cause of cancer death among African men. The analysis of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) can be utilized as a non-invasive tool for the diagnosis of PCa. In this study, we used small RNA sequencing to profile miRNAs cargo in plasma EVs from South African PCa patients. We evaluated the differential expression of miRNAs between low and high Gleason scores in the plasma EVs of South African patients and in the prostatic tissue from data available in the Cancer Genome Atlas (TCGA) Data Portal. We identified 7 miRNAs differently expressed in both EVs and prostatic tissues. We evaluated their expression using qPCR in a larger cohort of 10 patients with benign prostatic hyperplasia (BPH) and 24 patients with PCa. Here, we reported that the ratio between two of these miRNAs (i.e., miR-194-5p/miR-16-5p) showed a higher concentration in PCa compared to BPH and in metastatic PCa compared to localized PCa. We explored for the first time the profiling of miRNAs cargo in plasma EVs as a tool for the identification of putative markers in the South African population. Our finding indicated the ratio miR-194-5p/miR-16-5p as a non-invasive marker for the evaluation of PCa aggressiveness in this population.