Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer

Abstract

Background: It is becoming increasingly evident that microRNAs (miRNAs) are associated with the development and progression of prostate cancer (PCa).

Methods: We examined the hypothesis that plasma miRNA levels can differentiate patients by aggressiveness in 82 PCa patients. Taqman based quantitative RT-PCR assays were performed to measure copy number of target miRNAs.

Results: miR-20a was significantly overexpressed in plasma from patients with stage 3 tumors compared to stage 2 or below (P = 0.03). The expression levels for miR-20a and miR-21 were significantly increased in patients with high risk CAPRA scores (16,623 and 1,595 copies, respectively). Significantly increased miR-21 and miR-145 expression were observed for patients with intermediate or high risk D'Amico scores compared to patients with low risk scores (P = 0.047 and 0.011, respectively). The relapse rates for CAPRA scores ranged from 1.9% for low risk to 9.5% for intermediate risk and to 22.2% for high risk patients (P = 0.023). For D'Amico scores, the relapse rates ranged from 0.0% for low risk to 7.4% for intermediate risk and 17.6% for high risk patients (P = 0.039). Expression of miR-21 and miR-221 significantly differentiated patients with intermediate risk from those with low risk CAPRA scores (AUC = 0.801, P = 0.002). Four miRNAs (miR-20a, miR-21, miR-145, and miR-221) could also distinguish high versus low risk in PCa patients by D'Amico score with an AUC of 0.824.

Conclusions: These preliminary data suggest that altered plasma miRNAs may be useful predictors to distinguish PCa patients with varied aggressiveness. Further larger studies to validate this promising finding are warranted.

Conflict of interest statement

DISCLOSURE STATEMENT

The authors declare that no competing financial interests exist.

Copyright © 2012 Wiley Periodicals, Inc.

Figures

Fig. 1

Receiver-operator characteristic (ROC) curves plot of sensitive vs. 1 – specificity for plasma miRNAs expression (copy number/μl) and risk scores adjusted by age and ethnicity. A: ROC curve of miR-21 and miR-221 for intermediate vs. low risk of CAPRA score. An area under the curve (AUC) is 0.801 for the probability cut-point of 0.50 with a sensitivity of 38.1% (8/21) and a specificity of 94.2% (49/52). B: ROC curve of miR-20a, miR-21 and miR-145 for intermediate vs. low risk of D’Amico score. The AUC is 0.763 for the probability cut-point of 0.50 with a sensitivity of 44.4% (12/27) and a specificity of 86.8% (33/38). C: ROC curve of miR-20a, miR-21, miR-145 and miR-221 for high vs. low risk D’Amico score. The AUC is 0.824 for the probability cut-point of 0.50 with a sensitivity of 29.4% (5/17) and a specificity of 97.4% (37/38).