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Submitted on December 30, 2005
Revised on March 20, 2006
Accepted on March 21, 2006

Proteomics 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

Department of Biological Sciences, National University of Singapore, Singapore 117543

Corresponding Author: dbshead{at}nus.edu.sg

Colorectal cancer (CRC) is the second leading killer cancer worldwide and presently the most common cancer among males in Singapore. The study aims to detect changes of protein profiles associated with the process of colorectal tumorigenesis in order 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 (2-DE) at basic pH range (pH 7–10). Intensity changes of 34 spots were detected with statistical significance. 16 out 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 TCA cycle. Observed changes in protein abundance were verified by two-dimensional difference gel electrophoresis (2-D DIGE). These changes reveal an underlying mechanism of colorectal tumorigenesis in which the roles of impaired TCA cycle and Warburg effect may be critical.


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