Abstract
BackgroundBiochemical recurrence (BCR) is widely used to define the treatment success and to make decisions on if or how to initiate a secondary therapy, but uniform criteria to define BCR after radical prostatectomy (RP) is not yet completely assessed. UHRF1 has a unique function in regulating the epigenome by linking DNA methylation with histone marks. The clinical value of UHRF1 in PCa has not been well done. Therefore, we evaluated the prognostic significance of UHRF1.MethodUHRF1 expression in PCa cells was monitored by qRT-PCR and Western blot analyses. UHRF1 expression was knocked down using specific siRNAs, and the effects of knockdown on the proliferation, migration, cell cycle, and apoptosis of PCa cell lines were investigated. UHRF1 protein expression was evaluated in 225 PCa specimens using immunohistochemistry in tissue microarrays. Correlations between UHRF1 expression and the clinical features of PCa were assessed.ResultsThe results showed that UHRF1 was overexpressed in almost all of the PCa cell lines. In PCa cells, UHRF1 knockdown inhibited cell proliferation and migration, and induced apoptosis. UHRF1 expression levels were correlated with some clinical features of PCa. Multivariate analysis showed that UHRF1 expression was an independent prognostic factor for biochemical recurrence-free survival.ConclusionsUHRF1 functions as an oncogene in prostate cancer and appears to be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy, and may serve as a potential therapeutic target for PCa.
Highlights
Biochemical recurrence (BCR) is widely used to define the treatment success and to make decisions on if or how to initiate a secondary therapy, but uniform criteria to define BCR after radical prostatectomy (RP) is not yet completely assessed
Expression levels of UHRF1 mRNA and protein in Prostate cancer (PCa) cell lines The mRNA and protein expression levels of UHRF1 were evaluated in the human PCa cell lines 22RV1, DU145, PC3, and LNCaP by qRT-PCR and Western blot analyses, respectively (Fig. 1a-c)
We observed a significant increase of UHRF1 gene expression at both mRNA and protein levels in the transfected cells (Fig. 1j-l)
Summary
Biochemical recurrence (BCR) is widely used to define the treatment success and to make decisions on if or how to initiate a secondary therapy, but uniform criteria to define BCR after radical prostatectomy (RP) is not yet completely assessed. The clinical value of UHRF1 in PCa has not been well done. Since the advent of prostate-specific antigen (PSA) testing in the late 1980s, different diagnostic and treatment approaches for PCa have been developed [1]. BCR is widely used to define the treatment success and to make decisions on if or how to initiate a secondary therapy, but uniform criteria to define BCR after radical prostatectomy (RP) is not yet completely assessed. EAU guidelines define a PSA cutoff post-RP of ≥0.2 ng/ml [4]. EAU guidelines define BCR when two sequential PSA values post-
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