Epithelial and stromal expression of miRNAs during prostate cancer progression

Global microRNA (miRNA) profile may predict prostate cancer (PCa) behaviors. In this study, we examined global miRNA expression by miRNA profiling as well as specific miRNA expression levels in PCa epithelium and stoma by in situ hybridization (ISH) and correlated with various clinic pathological features. We first performed comprehensive miRNA profiling on 27 macro dissected cases of PCa by miRNA microarray. A total of 299 miRNAs were signifcantly dys regulated in high grade and advanced stage PCa. We demonstrated that PCa can be readily classi-fed into high grade/stage and low-grade/stage groups by its global miRNA expression profle. Next, we examined the expression of several selected dysregulated miRNAs, including let-7c, miR-21, miR-27a, miR-30c, and miR-219, in PCa by ISH. The levels of miRNA expression in epithelial and stromal cells were scored semiquanti tatively and compared with clinic pathological features, including age, race, Gleason score, stage, PSA recurrence, metastasis, hormone resistance and survival. We found that the expression of miR-30c and miR-219 were significantly down-regulated in PCa. miR-21 and miR-30c were significantly down-regulated in PCa in African Americans compared to Caucasian Americans. In addition, down-regulation of let-7c, miR-21, miR-30c, and miR-219 are associated with metastatic disease. Furthermore, down-regulation of miR-30c and let-7c are significantly associated with androgen-dependent PCa. In PCa stromal cells, let-7c down regulation is significantly associated with extraprostatic extension. Our data suggest that selected miRNAs may serve as potential biomarkers to predict cancer progression.