Novel diagnostic and prognostic classifiers for prostate cancer identified by genome-wide microRNA profiling.
OBJECTIVE
This study investigates the diagnostic and prognostic biomarker potential of miRNAs in prostate cancer (PC).


RESULTS
We identified several new deregulated miRNAs between non-malignant (NM) and PC tissue samples and between more/less aggressive PC subgroups. We also developed and validated a novel 13-miRNA diagnostic classifier with high sensitivity and specificity for PC. Finally, we trained a new 3-miRNA prognostic classifier (miR-185-5p+miR-221-3p+miR-326) that predicted time to biochemical recurrence (BCR) independently of routine clinicopathological variables in a training radical prostatectomy (RP) cohort (n = 126) as well as in two independent validation cohorts (n = 110 and n = 99).


METHODS
After RT-qPCR-based profiling of 752 miRNAs in 13 NM and 134 PC tissue samples (cohort 1), we selected 93 top candidate diagnostic/prognostic miRNAs for validation in two independent patient sets (cohort 2: 19 NM and 138 PC; cohort 3: 28 NM and 113 PC samples). Diagnostic potential was assessed by ROC curve analysis and prognostic potential by Kaplan-Meier, uni- and multivariate Cox regression analyses. BCR after RP was used as endpoint.


CONCLUSIONS
This is the first report of a miRNA signature with significant independent prognostic value demonstrated in three PC patient cohorts.
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.|Exiqon A/S, Skelstedet, Vedbaek, Denmark.
Helle
H
Kristensen
Exiqon A/S, Skelstedet, Vedbaek, Denmark.
Anni R
AR
Thomsen
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Christa
C
Haldrup
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Lars
L
Dyrskjøt
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Søren
S
Høyer
Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
Michael
M
Borre
Exiqon A/S, Skelstedet, Vedbaek, Denmark.
Peter
P
Mouritzen
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Torben F
TF
Ørntoft
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Karina Dalsgaard
KD
Sørensen
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D035683:MicroRNAs
biomarker; diagnosis; microRNA; prognosis; prostate cancer