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Molecular & Cellular Proteomics 5:1119-1130, 2006.
© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Proteomic Analysis of Colorectal Cancer Reveals Alterations in Metabolic Pathways

Mechanism of Tumorigenesis^*

Xuezhi Bi^,, Qingsong Lin^,,¶, Tet Wei Foo^,, Shashikant Joshi, Tao You, Han-Ming Shen^||, Choon Nam Ong^||, Peh Yean Cheah^**, Kong Weng Eu^** and Choy-Leong Hew^,

From the Department of Biological Sciences, National University of Singapore, Singapore 117543, ^|| Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore 117597, and ^** Department of Colorectal Surgery, Singapore General Hospital, 1 Hospital Drive, Singapore 169608, Singapore

Colorectal cancer is the second leading killer cancer worldwide and presently the most common cancer among males in Singapore. The study aimed to detect changes of protein profiles associated with the process of colorectal tumorigenesis to identify specific protein markers for early colorectal cancer detection and diagnosis or as potential therapeutic targets. Seven pairs of colorectal cancer tissues and adjacent normal mucosa were examined by two-dimensional gel electrophoresis at basic pH range (pH 7–10). Intensity changes of 34 spots were detected with statistical significance. 16 of the 34 spots were identified by MALDI-TOF/TOF tandem mass spectrometry. Changes in protein expression levels revealed a significantly enhanced glycolytic pathway (Warburg effect), a decreased gluconeogenesis, a suppressed glucuronic acid pathway, and an impaired tricarboxylic acid cycle. Observed changes in protein abundance were verified by two-dimensional DIGE. These changes reveal an underlying mechanism of colorectal tumorigenesis in which the roles of impaired tricarboxylic acid cycle and the Warburg effect may be critical.

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