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Báo cáo hóa học: " Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer"

Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer | Ehlén et al. Journal of Translational Medicine 2010 8 78 http www.translational-medicine.eom content 8 1 78 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer 1 2 1 P s PS z-s z- 2 3 1 Asa Ehlén Donal J Brennan Bjorn Nodin Darran P OConnor Jakob Eberhard Maria Alvarado-Kristensson I D I 4 I r h I X I r5 6 I V r D V 3 Z l I 1 h ỉ I r I I I zA 7 c VO I M s D Z X zA 8 u- I I I rr-ErAA m 1 Ian B Jeffrey Jonas Manjer Jenny Brcindstedt Mathias Uhién Fredrik Pontén Karin Jirstrom Abstract Background We 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. Methods RBM3 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. Results Increased 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 .