Circulating Mirna Signatures: A New Challenge In Castration-Resistant Prostate Cancer.

e16100 Background: The androgen receptor (AR) signaling pathway is involved in the emergence of castration-resistant prostate cancer (CRPC). Novel biomarkers are strongly needed to improve prediction for early detection of CRPC. Accumulating evidence has shown that specific microRNAs (miRNAs) serve key functional roles in prostate cancer (PC) cells. In this study we evaluated the role of miR-141 and miR-21, in PC transition to CRPC. Methods: A total of 24 consecutive patients (pts) affected by PC (12 hormone sensitive prostate cancer-HSPC and 12 CRPC) and 20 sex matched healthy controls were included in this preliminary analysis. The putative miR-141 and miR-21 binding sites were identified by means of common algorithms, validating the involvement of these microRNAs in androgen receptor signaling pathway. miRNAs profiling was performed using Real-Time PCR. P-values < 0.05 were considered statistically significant. Clinical and pathological data were collected. Results: The expression levels of miR-141 were increased by 3.7-fold in serum samples from PC patients in comparison with controls (p = 0.029). In particular, miR-141 levels were increased by 2.4-fold (p > 0.05) and 4.2-fold (p = 0.005) in HSPC and CRPC patients, respectively, compared with controls. Interestingly, the amounts of miR-141 were also found to be 1.9-fold increased in serum samples of CRPC patients when compared to HSPC patients (p = 0.038). miR-21 was also upregulated in serum samples obtained from prostate cancer patients in comparison to those of healthy subjects, but not significantly (1.7-fold, p > 0.05). In addition, no significant differences were observed in the expression levels of miR-21 between HSPC and CRPC patients. A positive correlation was recorded between PSA levels and miR-141 amounts ( p < 0.023). Conclusions: Our preliminary data confirm a potential role for circulating miR-141 in PC and androgen resistance. These preliminary findings support the future potential of miRNAs as early predictor of disease progression and castration resistance for PC. Further validations and investigations will be needed to better define their role as useful serum biomarkers.