Low RBM3 protein expression correlates with clinical stage, prognostic classification and increased risk of treatment failure in testicular non-seminomatous germ cell cancer.

Sven-Erik Olofsson,Mats Jerkeman,Karin Jirström,Alexander Gaber,Jakob Eberhard,Björn Nodin,Mathias Uhlén

doi:10.1371/journal.pone.0121300

Abstract

BackgroundExpression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate with favourable clinicopathological parameters and prognosis in several cancer diseases. The aim of this study was to examine the expression and prognostic ability of RBM3 in patients with testicular non-seminomatous germ cell tumours (NSGCT).Patients and MethodsImmunohistochemical RBM3 expression was analysed in tissue microarrays with tumours from 206 patients. Chi-square test was applied to analyze associations between RBM3 expression and clinicopathological parameters. Kaplan-Meier analysis was used to assess the impact of RBM3 expression on cancer-specific survival (CSS) and failure-free survival (FFS). Cox regression proportional hazards models were used to estimate the relative risk for failure.ResultsIn the entire cohort, there was a significant association between clinical stage (p=0.044) and RBM3 expression. Weak RBM3 expression correlated with a significantly reduced FFS [79.3% versus 90.4% (p=0.019)] and CSS [87.5% versus 97.3% (p=0.047)]. For patients with metastatic disease (n = 88), significant associations were found between RBM3 expression and IGCCC group (p=0.007). The FFS was significantly inferior for patients with low tumour-specific RBM3 expression [59.3% versus 79.0% (p=0.013)], and this association remained significant in a multivariable model for patients with metastatic disease (HR=3.67; 95% CI 1.14, 11.89).ConclusionLow RBM3 expression is an independent predictor of treatment failure in metastatic NSGCT, in relation to the prognostic factors included in the International Germ Cell Consensus Classification (IGCCC). These findings suggest that RBM3 may be a potential biomarker for treatment stratification in patients with metastatic non-seminomatous germ cell tumours, and therefore merit further validation.

Highlights

Since the introduction of cisplatin into the treatment of testicular cancer (TC), more than 95% of patients are cured
For patients with metastatic disease (n = 88), significant associations were found between RNA-binding motif protein 3 (RBM3) expression and International Germ Cell Consensus Classification (IGCCC) group (p=0.007)
The failure-free survival (FFS) was significantly inferior for patients with low tumour-specific RBM3 expression [59.3% versus 79.0% (p=0.013)], and this

Summary

Introduction

Since the introduction of cisplatin into the treatment of testicular cancer (TC), more than 95% of patients are cured. For patients without any evidence of metastatic disease, i.e. clinical stage I (CS I), survival approaches 100% [1, 2]. The International Germ Cell Consensus Classification (IGCCC) for non-seminomatous germ cell tumours (NSGCT)[3] is used to classify patients with metastatic disease into three groups with good, intermediate or poor prognosis, based on clinical parameters present prior to therapy (S1 Table). Certain clinicopathological factors have proven to be of value to guide treatment, there is a clear need for additional prognostic markers to better discriminate between patients with high-risk and low-risk disease[5]. The aim of this study was to examine the expression and prognostic ability of RBM3 in patients with testicular non-seminomatous germ cell tumours (NSGCT)

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