Stromal expression of MiR-21 predicts biochemical failure in prostate cancer patients with Gleason score 6.
OBJECTIVE
microRNAs (miRNAs) are involved in various neoplastic diseases, including prostate cancer (PCs). The aim of this study was to investigate the miRNA profile in PC tissue, to assess their association with clinicopathologic data, and to evaluate the potential of miRNAs as diagnostic and prognostic markers.


METHODS
From a cohort of 535 patients submitted to radical prostatectomy (RP), a sample of 30 patients (14 patients with rapid biochemical failure (BF) and 16 patients without BF) with Gleason score 7 were analyzed. A total of 1435 miRNAs were quantified by microarray hybridization, and selected miRNAs with the highest Standard deviation (n = 50) were validated by real-time quantitative PCR (qRT-PCR). In situ hybridization (ISH) was used to evaluate the expression of miR-21.


RESULTS
miR-21 was the only miR that was significantly up-regulated in the BF group (p = 0.045) miR-21 was up-regulated in patients with BF compared with non-BF group (p = 0.05). In univariate analyses, high stromal expression of miR-21 had predictive impact on biochemical failure-free survival (BFFS) and clinical failure-free survival (CFFS) (p = 0.006 and p = 0.04, respectively). In the multivariate analysis, high stromal expression of miR-21 expression was found to be an independent prognostic factor for BFFS in patients with Gleason score 6 (HR 2.41, CI 95% 1.06-5.49, p = 0.037).


CONCLUSIONS
High stromal expression of miR-21 was associated with poor biochemical recurrence-free survival after RP. For patients with Gleason score 6, miR-21 may help predict the risk of future disease progression and thereby help select patients for potential adjuvant treatment or a more stringent follow-up.
Department of Medical Biology, UIT The Arctic University of Norway, Tromsø, Norway.
Christian
C
Melbø-Jørgensen
Department of Medical Biology, UIT The Arctic University of Norway, Tromsø, Norway.
Nora
N
Ness
Department of Clinical Medicine, UIT The Arctic University of Norway, Tromsø, Norway; Department Oncology, University Hospital of North Norway, Tromsø, Norway.
Sigve
S
Andersen
Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Andrej
A
Valkov
Department of Clinical Medicine, UIT The Arctic University of Norway, Tromsø, Norway; Department Oncology, University Hospital of North Norway, Tromsø, Norway.
Tom
T
Dønnem
Department of Medical Biology, UIT The Arctic University of Norway, Tromsø, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Samer
S
Al-Saad
Department of Medical Biology, UIT The Arctic University of Norway, Tromsø, Norway; Department of Pharmacy, UIT The Arctic University of Norway, Tromsø, Norway.
Yury
Y
Kiselev
Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Thomas
T
Berg
Department of Clinical Medicine, UIT The Arctic University of Norway, Tromsø, Norway; Department of Urology, University Hospital of North Norway, Tromsø, Norway.
Yngve
Y
Nordby
Department of Clinical Medicine, UIT The Arctic University of Norway, Tromsø, Norway; Department Oncology, University Hospital of North Norway, Tromsø, Norway.
Roy M
RM
Bremnes
Department of Medical Biology, UIT The Arctic University of Norway, Tromsø, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Lill-Tove
LT
Busund
Department of Medical Biology, UIT The Arctic University of Norway, Tromsø, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Elin
E
Richardsen
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate
D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs