Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer.
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.
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, New York, USA. js2182@columbia.edu
Jing
J
Shen
Gregory W
GW
Hruby
James M
JM
McKiernan
Irina
I
Gurvich
Michael Jeffrey
MJ
Lipsky
Mitchell C
MC
Benson
Regina M
RM
Santella
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011795:Surveys and Questionnaires
D014408:Biomarkers, Tumor; D035683:MicroRNAs