Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer

Abstract

Background: Low nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to be associated with poor prognosis in several cancer forms e.g. breast, ovarian, colorectal, prostate cancer and malignant melanoma. The aim of this study was to examine the prognostic impact of RBM3 expression in urinary bladder cancer.

Methods: Immunohistochemical RBM3 expression was examined in tumours from 343 patients with urothelial bladder cancer. Chi-square and Spearman's correlation tests were applied to explore associations between RBM3 expression and clinicopathological characteristics. The impact of RBM3 expression on disease-specific survival (DSS), 5-year overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analysis and Cox proportional hazards modelling.

Results: Reduced nuclear RBM3 expression was significantly associated with more advanced tumour (T) stage (p <0.001) and high grade tumours (p=0.004). Negative RBM3 expression was associated with a significantly shorter DSS (HR=2.55; 95% CI 1.68-3.86)) and 5-year OS (HR=2.10; 95% CI 1.56-2.82), also in multivariable analysis (HR=1.65; 95% CI 1.07-2.53 for DSS and HR=1.54; 95% CI 1.13-2.10 for 5-year OS). In patients with Ta and T1 tumours expressing reduced RBM3 levels, Kaplan-Meier analysis revealed a significantly shorter PFS (p=0.048) and 5-year OS (p=0.006).

Conclusion: Loss of RBM3 expression is associated with clinically more aggressive tumours and an independent factor of poor prognosis in patients with urothelial bladder cancer and a potentially useful biomarker for treatment stratification and surveillance of disease progression.

Figure 1

Sample immunohistochemical images of RBM 3 staining in urothelial bladder cancer. Images (20x magnification) representing (a) negative, (b) intermediate and (c) high nuclear RBM3 expression.

Figure 2

Kaplan-Meier estimates of bladder cancer specific survival and 5-year overall survival in the full cohort. Kaplan-Meier analysis of (a) bladder cancer specific and (b) overall survival in strata of negative, intermediate and high RBM3 expression.

Figure 3

Kaplan-Meier estimates of progression free survival and 5-year overall survival in patients with Ta and T1 tumours. Kaplan-Meier analysis of progression free survival in strata according to (a) negative, intermediate and high RBM3 expression and (b) negative-intermediate versus high expression, and 5-year overall survival in (c) negative, intermediate and high RBM3 expression and (d) negative versus positive expression.