Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancerReport as inadecuate




Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer - Download this document for free, or read online. Document in PDF available to download.

Journal of Translational Medicine

, 8:78

First Online: 20 August 2010Received: 14 April 2010Accepted: 20 August 2010DOI: 10.1186-1479-5876-8-78

Cite this article as: Ehlén, Å., Brennan, D.J., Nodin, B. et al. J Transl Med 2010 8: 78. doi:10.1186-1479-5876-8-78

Abstract

BackgroundWe recently demonstrated that increased expression of the RNA-binding protein RBM3 is associated with a favourable prognosis in breast cancer. The aim of this study was to examine the prognostic value of RBM3 mRNA and protein expression in epithelial ovarian cancer EOC and the cisplatin response upon RBM3 depletion in a cisplatin-sensitive ovarian cancer cell line.

MethodsRBM3 mRNA expression was analysed in tumors from a cohort of 267 EOC cases Cohort I and RBM3 protein expression was analysed using immunohistochemistry IHC in an independent cohort of 154 prospectively collected EOC cases Cohort II. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between RBM3 and recurrence free survival RFS and overall survival OS. Immunoblotting and IHC were used to examine the expression of RBM3 in a cisplatin-resistant ovarian cancer cell line A2780-Cp70 and its cisplatin-responsive parental cell line A2780. The impact of RBM3 on cisplatin response in EOC was assessed using siRNA-mediated silencing of RBM3 in A2780 cells followed by cell viability assay and cell cycle analysis.

ResultsIncreased RBM3 mRNA expression was associated with a prolonged RFS HR = 0.64, 95% CI = 0.47-0.86, p = 0.003 and OS HR = 0.64, 95% CI = 0.44-0.95, p = 0.024 in Cohort I. Multivariate analysis confirmed that RBM3 mRNA expression was an independent predictor of a prolonged RFS, HR = 0.61, 95% CI = 0.44-0.84, p = 0.003 and OS HR = 0.62, 95% CI = 0.41-0.95; p = 0.028 in Cohort I. In Cohort II, RBM3 protein expression was associated with a prolonged OS HR = 0.53, 95% CI = 0.35-0.79, p = 0.002 confirmed by multivariate analysis HR = 0.61, 95% CI = 0.40-0.92, p = 0.017. RBM3 mRNA and protein expression levels were significantly higher in the cisplatin sensitive A2780 cell line compared to the cisplatin resistant A2780-Cp70 derivative. siRNA-mediated silencing of RBM3 expression in the A2780 cells resulted in a decreased sensitivity to cisplatin as demonstrated by increased cell viability and reduced proportion of cells arrested in the G2-M-phase.

ConclusionsThese data demonstrate that RBM3 expression is associated with cisplatin sensitivity in vitro and with a good prognosis in EOC. Taken together these findings suggest that RBM3 may be a useful prognostic and treatment predictive marker in EOC.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-8-78 contains supplementary material, which is available to authorized users.

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Author: Åsa Ehlén - Donal J Brennan - Björn Nodin - Darran P O-Connor - Jakob Eberhard - Maria Alvarado-Kristensson - Ian B J

Source: https://link.springer.com/







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