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The discovery and validation of colorectal cancer biomarkers

Authors

  • Ching-Seng Ang,

    1. Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Melbourne, Australia
    2. Department of Primary Industries, Biosciences Research Division, Victorian AgriBiosciences Centre, Bundoora, Australia
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  • Jason Phung,

    1. Monash University, Department of Biochemistry, Melbourne, Australia
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  • Edouard C. Nice

    Corresponding author
    1. Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Melbourne, Australia
    2. The University of Melbourne, Melbourne, Australia
    3. Monash University, Department of Biochemistry, Melbourne, Australia
    • Clinical Biomarker Discovery and Validation, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
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  • Abbreviations used: CRC, colorectal cancer; CCAP, colorectal cancer associated protein; CEA, carcinoembryonic antigen; CT, computed tomography; FOBT, faecal occult blood test; FS, flexible sigmoidoscopy; IMAC, immobilized metal affinity chromatography; MALDI, matrix-assisted laser desorption/ionization; MRM, multiple reaction monitoring; SELDI, surface enhanced laser desorption and ionization time-of-flight mass spectrometry; QQQ, triple quadrupole; SEC, size exclusion chromatography

Abstract

Colorectal cancer is currently the third most common malignancy in the world. Patients have excellent prognosis following surgical resection if their tumour is still localized at diagnosis. By contrast, once the tumour has started to metastasize, prognosis is much poorer. Accurate early detection can therefore significantly reduce the mortality from this disease. However, current tests either lack the required sensitivity and selectivity or are costly and invasive. Improved biomarkers, or panels of biomarkers, are therefore urgently required. We have addressed current screening strategies and potential protein biomarkers that have been proposed. The role of both discovery and hypothesis-driven proteomics approaches for biomarker discovery and validation is discussed. Using such approaches we show how multiple reaction monitoring (MRM) can be successfully developed and used for quantitative multiplexed analysis of potential faecal biomarkers. Copyright © 2010 John Wiley & Sons, Ltd.

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