Title: Downregulation of mir-221 is a strong and independent predictor of clinical progression and css in high-risk prostate cancer
Authors: Spahn, M
Joniau, Steven
Kneitz, S
Scholz, C. J
Schubert, M
Kalogiru, C
Lerut, Evelyne
Stroebel, P
Van Poppel, Hendrik
Riedmiller, H
Kneitz, B #
Issue Date: Mar-2011
Publisher: Elsevier science bv
Host Document: European urology supplements vol:10 issue:2 pages:238-239
Conference: EAU Annual Congress edition:26 location:Vienna, Austria date:18-22 March 2011
Article number: 749
Abstract: Introduction & Objectives: MicroRNAs (miR) are non-coding, single-stranded RNAs that repress target mRNA translation to control various biological processes. MiR expression profiles have been linked to the clinical features of several cancers including prostate carcinoma (PCa). We recently described miR-221 as a new biomarker to predict clinical progression in high-risk Prostate cancer. This study aimed to proof the value of miR-221 downregulation as a predictor of clinical progression and cancer specific survival (CSS) in clinical localised high-risk PCa
patients treated with radical prostatectomy (RP) in two independent cohorts.

Materials & Methods: We analysed the expression of miR-221 by qRT-PCR in men with clinical high risk prostate cancer (defined as either PSA>20 ng/ml or cT3/cT4 or biopsy Gleason 8-10) to validate the associations between the expression of miR-221, various clinicopathologic factors, and patient survival in two independent well defined high risk PCa cohorts. Group 1 was treated at the University hospital Würzburg and included 124 patients. Group 2 included 92 high-risk PCa patients derived from UZ Leuven.

Results: MiR-221 was progressively down-regulated in aggressive forms of prostate carcinoma. Kaplan Meier estimates and Cox proportional hazard models showed that miR-221 down-regulation was linked to tumor progression, clinical recurrence and cancer related death in both high risk prostate cancer cohorts. (Univariate analysis : Time to clinical failure: Group 1: p<0.00001, HR 0,36
(95%CI 0.23 to 0,56) and group 2: p<0,0001, HR 0,33 (95% CI 0,19 to 0,57). Cancer related death: Group 1: p= 0,004, HR 0,46 (95% CI 0,27to 0,78) and Group 2: p<0,0001, HR 0,32 (95%CI 0,19 to 0,56) and group 2: p<0,00001, HR 0,18
(95% CI 0,083 to 0,39). In the multivariable model miR-221 was confirmed as an independent predictor for both, clinical progression and cancer related death (group 1: p=0,0045, HR 0,46 (95%CI 0,27 to 0,79) and P=0,014, HR 0,43 (95% CI 0,21 to 0,84), respectively. Group 2: p=0,051, HR 0,49 (95%CI 0,24 to 1,0) and p<0,001 HR 0,66 (95%CI 0,013 to 0,33), respectively.

Conclusions: This first external validation study confirmed that miR-221 downregulation presents a novel prognostic marker in high-risk prostate carcinoma. The functional role of miR-221 and its relevance for cell growth control suggests that miR-221 has potential as a diagnostic marker and therapeutic target in prostate carcinoma.
ISSN: 1569-9056
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Urology Section (-)
Translational Cell & Tissue Research
# (joint) last author

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