UHRF1 overexpression is involved in cell proliferation and biochemical recurrence in prostate cancer after radical prostatectomy

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.

The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer

“…Mean biochemical recurrence (BCR) free time in UHRF1-positive patients was around 23.0 months versus 38.9 months in UHRF1-negative patients while 5-year BCR-free survival rate was 12.4% in UHRF1-positive patients as compared with 51.8% in UHRF1-negative patients. These results support UHRF1 as a valuable independent prognostic factor to predict prostate cancer outcome after radical prostatectomy [ 109 ].…”

“…This overexpression correlated with poor clinical prognosis as patients with high expression of UHRF1 had reduced median survival rates (10.4 years) as compared to patients with low expression of UHRF1 (12.4 years) [ 108 ]. Recently Wan et al reported similar results after analyzing expression of UHRF1 in 225 prostate cancer specimens [ 109 ]. UHRF1 staining was found in 47.1% of specimens which positively correlated with the Gleason score and the pathological stage of the disease [ 109 ].…”

“…Recently Wan et al reported similar results after analyzing expression of UHRF1 in 225 prostate cancer specimens [ 109 ]. UHRF1 staining was found in 47.1% of specimens which positively correlated with the Gleason score and the pathological stage of the disease [ 109 ]. Patients with higher levels of UHRF1 were found to be at higher risk for biochemical recurrence after radical prostatectomy.…”

“…At the cellular level, overexpression of UHRF1 has also been reported in aggressively proliferating, androgen-independent cell lines of prostate cancer (DU145 and PC3), while low expression of UHRF1 was found in immortalized normal prostate epithelial cells (LHS) or androgen-dependent prostate adenocarcinoma cells with low metastatic potential (LNCaP and 22Rv1 cells) [ 108 , 109 ]. Overexpression of UHRF1 accompanied with downregulation of tumor suppressor genes and increased expression of EZH2 (H3K27 methyltransferase) in prostate cancer cells contributed to the poor clinical prognosis and lethal progression disease.…”

Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer

“…Currently, with the use of prostate-specific antigen (PSA) and prostate biopsy for prostate cancer screening, more and more patients can be diagnosed in the early stage and treated by radical prostatectomy [ 3 , 4 ]. However, about 25–50% of prostate cancer patients will have tumor recurrence after surgery, and many will die of the cancer [ 5 , 6 ]. Although current clinicopathological features such as Gleason score, disease stage, and PSA level provide important information, they do not accurately predict an individual patient’s prognosis, and new biomarkers are needed for prognostication [ 7 , 8 ].…”