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Identification of Clinically Relevant Protein Targets in Prostate Cancer with 2D-DIGE Coupled Mass Spectrometry and Systems Biology Network Platform

Author

Listed:
  • Ramesh Ummanni
  • Frederike Mundt
  • Heike Pospisil
  • Simone Venz
  • Christian Scharf
  • Christine Barett
  • Maria Fälth
  • Jens Köllermann
  • Reinhard Walther
  • Thorsten Schlomm
  • Guido Sauter
  • Carsten Bokemeyer
  • Holger Sültmann
  • A Schuppert
  • Tim H Brümmendorf
  • Stefan Balabanov

Abstract

Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.

Suggested Citation

  • Ramesh Ummanni & Frederike Mundt & Heike Pospisil & Simone Venz & Christian Scharf & Christine Barett & Maria Fälth & Jens Köllermann & Reinhard Walther & Thorsten Schlomm & Guido Sauter & Carsten Bok, 2011. "Identification of Clinically Relevant Protein Targets in Prostate Cancer with 2D-DIGE Coupled Mass Spectrometry and Systems Biology Network Platform," PLOS ONE, Public Library of Science, vol. 6(2), pages 1-14, February.
    • Handle: RePEc:plo:pone00:0016833
    DOI: 10.1371/journal.pone.0016833
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    References listed on IDEAS

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    1. H. Jeong & S. P. Mason & A.-L. Barabási & Z. N. Oltvai, 2001. "Lethality and centrality in protein networks," Nature, Nature, vol. 411(6833), pages 41-42, May.
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    1. Stefan Balabanov & Thomas Wilhelm & Simone Venz & Gunhild Keller & Christian Scharf & Heike Pospisil & Melanie Braig & Christine Barett & Carsten Bokemeyer & Reinhard Walther & Tim H Brümmendorf & And, 2013. "Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-14, January.

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