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High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer

Author:
  • Barbara Hjelm
  • Donal J. Brennan
  • Nooreldin Zendehrokh
  • Jakob Eberhard
  • Björn Nodin
  • Alexander Gaber
  • Fredrik Ponten
  • Henrik Johannesson
  • Kristina Smaragdi
  • Christian Frantz
  • Sophia Hober
  • Louis Banka Johnson
  • Sven Påhlman
  • Karin Jirström
  • Mathias Uhlen
Publishing year: 2011
Language: English
Pages: 624-635
Publication/Series: Proteomics Clinical Applications
Volume: 5
Issue: 11-12
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

Purpose: In this study, we investigated the prognostic impact of human RBM3 expression in colorectal cancer using tissue microarray-based immunohistochemical analysis. Experimental design: One polyclonal antibody and four monoclonal anti-RBM3 antibodies were generated and epitope mapped using two different methods. Bacterial display revealed five distinct epitopes for the polydonal antibody, while the four mouse monoclonal antibodies were found to bind to three of the five epitopes. A peptide suspension bead array assay confirmed the five epitopes of the polydonal antibody, while only one of the monoclonal antibodies could be mapped using this approach. Antibody specificity was confirmed by Western blotting and immunohistochemistry, including siRNA-mediated knock-down. Two of the antibodies (polydonal and monoclonal) were subsequently used to analyze RBM3 expression in tumor samples from two independent colorectal cancer cohorts, one consecutive cohort (n = 270) and one prospectively collected cohort of patients with cancer of the sigmoid colon (n = 305). RBM3-expression was detected, with high correlation between both antibodies (R = 0.81, p < 0.001). Results: In both cohorts, tumors with high nuclear RBM3 staining had significantly prolonged the overall survival. This was also confirmed in multivariate analysis, adjusted for established prognostic factors. Conclusion and clinical relevance: These data demonstrate that high tumor-specific nuclear expression of RBM3 is an independent predictor of good prognosis in colorectal cancer.

Keywords

  • Cell and Molecular Biology
  • Antibodies
  • Colorectal cancer
  • Epitope mapping
  • Prognosis
  • RNA-binding
  • protein

Other

Published
  • Pathology, Malmö
  • Surgery Research
  • ISSN: 1862-8354
Sven Påhlman
E-mail: sven [dot] pahlman [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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