The patient records was anonymized and de-identified prior to analysis. In this study, we found a higher expression of miR-21 in cancer tissues compared with normal prostatic tissue. The expression was highest in tumor stromal areas. High tumor stromal expression of miR-21 was an independent prognostic factor for biochemical failure in patients with Gleason grade 6 but not clinical failure, probably due to few events in the latter group. To our knowledge, this is the first study reporting tumor stromal expression of miR-21 as a prognostic marker for BF after radical prostatectomy. Moreover, we also found a high stromal expression to be an independent marker for PSM in RP specimens. Recent studies have shown that miRNAs are significantly altered in prostate cancer, suggesting that miRNAs act as key regulators of prostate carcinogenesis. Several studies have been conducted to identify the PC-specific miRNA signature, but n consensus has been reached with respect to miRNAs role in development and progression of PC. In a study by Violinia et al., total RNA was extracted from 363 solid cancers, including prostate cancer, and 177 normal tissues.

They found a general up-regulation of 39 miRNAs, including miR-21, whereas 6 miRNAs were down-regulated. These results were in partial agreement with a study by Ambs et al. in which total RNA extracted from 60 micro-dissected PC and 16 surrounding nontumor tissues were analyzed. MiR-21 is generally considered an oncogene, but so far its role in PC is unclear and the reports have been conflicting. miR-21 has been found to be elevated in PC3 and DU145 androgen-independent cell lines. Moreover, miR-21 was identified as an androgen receptorregulated miRNA whose level was elevated in PC compared with adjacent normal tissue. Inhibitions of miR-21 diminish androgen-induced PC cell proliferation, whereas elevated expression of miR-21 promotes enhanced tumor growth and castration resistance in vivo. Others have also found miR-21 upregulated in patients with NVP-BEZ235 hormone- and chemoresistant PC. We found that a high tumor stromal expression of miR-21 in tumors with Gleason score 6 predicted BF.

This is in line with previous reports. Stromal miR-21 expression analysis may be a potential tool to predict which highly differentiated tumors that is most likely to progress. Recent studies have provided valuable insights in clarifying the involment of miR-21 in tumor microenvironment: Bullock et al. demonstrated that upregulated miR21 expression occurs in cancer-associated stromal cells but not in colo-rectal cancer cells. Moreover, they found that ectopic miR-21 expression in fibroblasts modulated the cytotoxic impact of Oxaliplatin which resulted in cancer progression. Bronisz et al. demonstrated that downregulation of mir-320 in mammary stromal fibroblasts reprograms the tumor microenvironment by activating a pro-oncogenic secretome, and interestingly, Yao et al. reported that myofibroblast transdifferentiation from progenitor fibroblasts in response to TGF-b could be prevented using specific antisense inhibitors of miR-21.