Expression of RABEX-5 and its clinical significance in prostate cancer

Hongtuan Zhang,Shiyong Qi,Ranlu Liu,Can Qi,Yong Xu,Andi Wang,Bing Yao,Shang Cheng,Hui Ma

doi:10.1186/1756-9966-33-31

Abstract

BackgroundWhile recent research has shown that expression of RABEX-5 in breast cancer and colorectal cancer has a crucial impact on tumor development, there is little information regarding RABEX-5 expression in prostate cancer. This study investigated the expression of RABEX-5 in prostate cancer by real time quantitative polymerase chain reaction and evaluated its association with clinicopathological variables, including prostate cancer patient prognosis.MethodsA total of 180 patients with primary prostate cancer treated by radical prostatectomy were enrolled. Real time quantitative polymerase chain reaction was utilized to investigate mRNA expression level of RABEX-5 in 180 paired prostate cancer/adjacent non-cancerous tissues. RABEX-5 mRNA expression was divided into high expression group and low expression group and correlations between RABEX-5 mRNA and clinicopathological factors were then evaluated. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between RABEX-5 mRNA expression and prognosis of patients with prostate cancer.ResultsOur study showed that RABEX-5 mRNA was significantly upregulated in prostate cancer tissues. The data indicated that high expression of RABEX-5 mRNA was significantly associated with lymph node metastasis (P = 0.001), clinical stage (P = 0.004), biochemical recurrence (P = 0.009), preoperative prostate-specific antigen (P < 0.001), and Gleason score (P < 0.001). High RABEX-5 mRNA expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis.ConclusionThis is to our knowledge the first report investigating tumor RABEX-5 mRNA expression level in prostate cancer. We have shown that high RABEX-5 mRNA expression is a strong predictor of poor prognosis in prostate cancer patients treated by radical prostatectomy, and multivariate analysis confirmed RABEX-5 mRNA as an independent prognostic factor.

Highlights

While recent research has shown that expression of RABEX-5 in breast cancer and colorectal cancer has a crucial impact on tumor development, there is little information regarding RABEX-5 expression in prostate cancer
RABEX-5 mRNA expression is up-regulated in prostate cancer tissues compared to adjacent noncancerous tissues Abnormally high RABEX-5 expression has been implicated in colorectal cancer and breast cancer, but the pathological function of RABEX-5 in prostate cancer has not been well defined
Relationship between RABEX-5 mRNA expression and prostate cancer patients’ clinicopathological variables The annotation of 180 prostate cancer patients includes clinical outcomes, and in particular survival and biochemical recurrence data, so we cross-checked these data with RABEX-5 mRNA expression levels

Summary

Introduction

While recent research has shown that expression of RABEX-5 in breast cancer and colorectal cancer has a crucial impact on tumor development, there is little information regarding RABEX-5 expression in prostate cancer. Rabs function as a molecular switch by cycling between two nucleotide-bound states, a GDP-bound inactive state (“OFF” state) and a GTP-bound active state (“ON” state). Rabs are activated by specific guanine nucleotide exchange factors, which promote the release of GDP from Rab and binding of GTP to Rab, and the activated Rabs are inactivated by GTPase-activating proteins or spontaneously inactivated by their intrinsic GTPase activity [6], either of which terminates the cycle [6,7]. The identification and characterization of these Rab regulators, especially of GEFs, is crucial to understanding the spatiotemporal regulation of Rab GTPase activation

Methods

Results

Conclusion