Proteomic comparison of colorectal tumours and non-neoplastic mucosa from paired patient samples using iTRAQ mass spectrometry

Lucy Jankova, Charles Chan, Caroline L. S. Fung, Xiaomin Song, Sun Y. Kwun, Mark J. Cowley, Warren Kaplan, Owen F. Dent, Elie L. Bokey, Pierre H. Chapuis, Mark S. Baker, Graham R. Robertson, Stephen J. Clarke, Mark P. Molloy*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Quantitative mass spectrometry using iTRAQ was used to identify differentially expressed proteins from 16 colorectal cancer (CRC) tumours compared to patient-paired adjacent normal mucosa. Over 1400 proteins were identified and quantitated, with 118 determined as differentially expressed by >1.3-fold, with false discovery rate < 0.05. Gene Ontology analysis indicated that proteins with increased expression levels in CRC tumours include those associated with glycolysis, calcium binding, and protease inhibition. Proteins with reduced levels in CRC tumours were associated with loss of ATP production through: (i) reduced β-oxidation of fatty acids, (ii) reduced NADH production by the tricarboxylic acid cycle and (iii) decreased oxidative phosphorylation activity. Additionally, biosyntheses of glycosaminoglycans and proteoglycans were significantly reduced in tumour samples. Validation experiments using immunoblotting and immunohistochemistry (IHC) showed strong concordance with iTRAQ data suggesting that this workflow is suitable for identifying biomarker candidates. We discuss the uses and challenges of this approach to generate biomarker leads for patient prognostication.

Original languageEnglish
Pages (from-to)2997-3005
Number of pages9
JournalMolecular BioSystems
Volume7
Issue number11
DOIs
Publication statusPublished - 1 Nov 2011

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