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miR-21 as an Independent Biochemical Recurrence Predictor and Potential Therapeutic Target for Prostate Cancer
Ist Teil von
The Journal of urology, 2012-04, Vol.187 (4), p.1466-1472
Ort / Verlag
New York, NY: Elsevier Inc
Erscheinungsjahr
2012
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Purpose Abnormal miRNA expression is associated with prostate cancer progression. However, the relationship between miRNA and biochemical recurrence after radical prostatectomy is not well established. Thus, we evaluated the miRNA miR-21 as a biomarker to predict the risk of biochemical failure, and as a potential drug target for prostate cancer therapy. Materials and Methods miR-21 levels were assayed using locked nucleic acid in situ hybridization coupled with tissue microarray techniques in 169 radical prostatectomy tissue samples. The Cox proportional hazard model was used to analyze miR-21 expression as an independent predictor of biochemical recurrence. The association of miR-21 with recurrence was estimated using the Kaplan-Meier method. miR-21 was also evaluated as a potential drug target for prostate cancer therapy. Results miR-21 expression in prostate cancer tissue samples was significantly associated with pathological stage, lymph node metastasis, capsular invasion, organ confined disease, Gleason score, biochemical recurrence and patient followup. Multivariate analysis also indicated that miR-21 expression could be an independent predictor of biochemical recurrence. The 5-year recurrence-free probability for patients positive vs negative for miR-21 expression was 33.9% vs 44.5%. In vivo treatment with antagomir-21 also repressed the tumor growth of DU145 cells in nude mice. Conclusions Positive miR-21 expression was associated with poor biochemical recurrence-free survival and predicted the risk of biochemical recurrence in patients with prostate cancer after radical prostatectomy. Accordingly gene therapy using miR-21 inhibition strategies may prove useful for prostate cancer therapy.