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Cellular Oncology
Volume 30 (2008), Issue 1, Pages 13-26
http://dx.doi.org/10.1155/2008/686940

Differential Proteomic Analysis of Nuclear Matrix in Muscle-Invasive Bladder Cancer: Potential to Improve Diagnosis and Prognosis

Paola Barboro,1 Alessandra Rubagotti,1,2 Paola Orecchia,3 Bruno Spina,1 Mauro Truini,1 Erica Repaci,1 Giorgio Carmignani,4 Andrea Romagnoli,4 Carlo Introini,1 Francesco Boccardo,1,2 Barbara Carnemolla,1 and Cecilia Balbi1

1National Cancer Research Institute, Genoa, Italy
2Department of Oncology, Biology and Genetics, University of Genoa, Italy
3Institute Giannina Gaslini, Genoa, Italy
4Department of Urology, University of Genoa, Italy

Copyright © 2008 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction: Although several molecular markers for bladder cancer have been identified, at present little information on prognostic biomarkers is available in the literature. Prognostication of this tumor is largely based on clinicopathological characteristics. Our aim was to identify nuclear matrix (NM) proteins that might serve to better characterize the phenotype of the invasive bladder cancer and to investigate their diagnostic and prognostic roles.

Methods: NM proteins expressed in normal (n=3) or non-tumoral (n=9) tissue specimens and muscle-invasive bladder cancer (n=21) specimens were analyzed by two dimensional (2D) gel electrophoresis. PDQuest image analysis software was used to generate a comparative NM proteome analysis. Selected spots were characterized by liquid chromatography coupled to tandem mass spectrometry and Western blot.

Results: We detected over 800 protein spots in each 2D map and 43 spots were identified. 30 proteins were differentially expressed by bladder tumor cells; among these, 19 proteins were detected in bladder tumoral tissues but not in normal and non-tumoral tissues and seven proteins correlated with tumor stage. One protein (p54nrb) was strongly correlated with vascular invasions and appeared to be also significantly (P <0.0001) associated with a decreased probability of survival.

Conclusion: Important alterations in NM proteins occur in muscle-invasive bladder cancer. The differentially expressed proteins include biomarkers potentially useful for disease diagnosis, progression and prognosis. Our findings beyond improving the understanding of the biology of bladder cancer, could help to stratify patients into different prognostic subgroups and to select those who might be better candidate to multimodal therapeutic approaches.