Identification of biomarkers for colorectal cancer through proteomics-based approaches

Abstract

The early detection of colorectal cancer is one of the great challenges in the battle against this disease. However, owing to its heterogeneous character, single markers are not likely to provide sufficient diagnostic power to be used in colorectal cancer population screens. This review provides an overview of recent studies aimed at the discovery of new diagnostic protein markers through proteomics-based approaches. It indicates that studies that start with the proteomic analysis of tumor tissue or tumor cell lines (near the source) have a high potential to yield novel and colorectal cancer-specific biomarkers. In the next step, the diagnostic accuracy of these candidate markers can be assessed by a targeted ELISA assay using serum from colorectal cancer patients and healthy controls. Instead, direct proteomic analysis of serum yields predominantly secondary markers composed of fragments of abundant serum proteins that may be associated with tumor-associated protease activity, and alternatively, immunoproteomic analysis of the serum antibody repertoire provides a valuable tool to identify the molecular imprint of colorectal cancer-associated antigens directly from patient serum samples. The latter approach also allows a relatively easy translation into targeted assays. Eventually, multimarker assays should be developed to reach a diagnostic accuracy that meets the stringent criteria for colorectal cancer screening at the population level.

Keywords::

• cancer
• colorectal cancer
• diagnostics
• mass spectrometry
• proteomics

Acknowledgements

The author would like to thank Annemarie Boleij, Rian Roelofs, Coby Laarakkers, Dorine Swinkels and Yuri van den Burgt for useful discussions.

Financial & competing interests disclosure

The financial support of the Dutch Cancer Society (KWF kankerbestrijding; KUN-2006-3591) for our work on innovative CRC diagnostics is warmly acknowledged. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.