Proteomics in colorectal cancer translational research: Biomarker discovery for clinical applications

Colorectal cancer (CRC) is a major cause of cancer-related death in the western world. Screening to detect the disease in an early stage is the most effective approach to tackle this problem. In addition, better diagnostic tools for assessment of prognosis and prediction of response to drug therapy will allow for personalized therapies and better outcomes. Protein biomarkers that reflect tumor biology have the potential to address a wide range of clinical needs. These include diagnostic (screening) biomarkers for early detection, prognostic biomarkers for estimation of disease outcome, predictive biomarkers for adjuvant treatment stratification, and surveillance biomarkers for disease monitoring and treatment response. An important source for the discovery of potential biomarkers comes from mass spectrometry based proteomics research of the biology of CRC development.Here, we review recent colon cancer proteomics studies directed at identification of biomarker proteins. These include studies that use preclinical models (i.e. cell lines or murine tissues) as well as clinical materials (e.g. tissue and stool samples). We separately highlight some studies that focused on identification of cancer stem cell (CSC) related proteins in tumor spheroids, an in vitro model system for investigating CRC treatment response.Recent proteomics studies have generated many new candidate protein biomarkers. However, the lack of follow-up studies that lead to biomarker verification and/or validation remains a limiting factor in the translation of these candidate biomarkers into clinical applications. This is partly due to technological limitations which are bound to diminish with new technologies, including selected reaction monitoring mass spectrometry (SRM-MS). Antibodies are still required, though, both to perform high-throughput validation as well as to develop cost-effective tests for routine use in a clinical setting.

► Distinct clinical needs of CRC can be addressed with specific protein biomarkers.
► MS-based proteomics is widely applied for discovery of protein biomarkers for CRC.
► Most biomarkers still await validation due to lack of suitable assays and samples.
► Tools like SRM and HPA antibodies will boost validation for clinical applications.