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结直肠癌的蛋白质组学分析揭示了代谢途径的改变:肿瘤发生机制

Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways: mechanism of tumorigenesis.

作者信息

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

机构信息

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

出版信息

Mol Cell Proteomics. 2006 Jun;5(6):1119-30. doi: 10.1074/mcp.M500432-MCP200. Epub 2006 Mar 21.

Abstract

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.

摘要

结直肠癌是全球第二大致命癌症,目前是新加坡男性中最常见的癌症。该研究旨在检测与结直肠肿瘤发生过程相关的蛋白质谱变化,以识别用于早期结直肠癌检测和诊断的特定蛋白质标志物,或作为潜在的治疗靶点。通过在碱性pH范围(pH 7-10)进行二维凝胶电泳,对7对结直肠癌组织和相邻正常黏膜进行了检查。检测到34个斑点的强度变化具有统计学意义。通过基质辅助激光解吸电离飞行时间串联质谱法(MALDI-TOF/TOF)鉴定了34个斑点中的16个。蛋白质表达水平的变化显示糖酵解途径(瓦伯格效应)显著增强、糖异生减少、葡萄糖醛酸途径受抑制以及三羧酸循环受损。通过二维差异凝胶电泳(2D-DIGE)验证了观察到的蛋白质丰度变化。这些变化揭示了结直肠肿瘤发生的潜在机制,其中三羧酸循环受损和瓦伯格效应的作用可能至关重要。

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