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Open Access Highly Accessed Research article

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

Karolina Boman1*, Ulrika Segersten2, Göran Ahlgren3, Jakob Eberhard4, Mathias Uhlén56, Karin Jirström1 and Per-Uno Malmström2

Author Affiliations

1 Department of Clinical Sciences, Division of Pathology, Lund University, Skåne University Hospital, Lund, 221 85, Sweden

2 Department of Surgical Sciences, Uppsala University, Uppsala, 751 85, Sweden

3 Department of Clinical Sciences, Division of Urological Cancers, Lund University, Skåne University Hospital, Malmö, 205 02, Sweden

4 Department of Clinical Sciences, Division of Oncology, Lund University, Skåne University Hospital, Lund, 221 85, Sweden

5 Science for Life Laboratory and School of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm, 106 91, Sweden

6 School of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm, 106 91, Sweden

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BMC Urology 2013, 13:17  doi:10.1186/1471-2490-13-17

Published: 8 April 2013

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.

Keywords:
RBM3; Urothelial bladder cancer; Prognosis