The Role of Proteomics in Colorectal Cancer Biomarker Discovery
Colorectal cancer is one of the most prevalent cancers within the UK and has a steadily rising incidence. If detected early Colorectal Cancer (CRC) is highly curable, but currently only 9% of patients present when the cancer is in the earliest stages (Dukes Stage A). The unique characteristics of the disease render CRC a suitable model for population screening. Current screening modalities have proven utility but they lack sensitivity and specificity, and thus there is a need to develop non-invasive tests to detect and stage the disease. Biomarkers are gaining popularity as they provide a unique biological signature for the disease, and thus there has been increased expansion in the use of Proteomic technologies to undertake such research. The primary aim of this thesis was to apply proteomic techniques to analyze serum of patients with CRC, and thus develop novel biomarkers to aid in the diagnosis of CRC within a screening population. Prior to undertaking this, I firstly developed a reproducible and standardized pathway for biomarker verification using 2 proteomic platforms – iTRAQ and label free. I identified that the use of depletion methods along with iTRAQ and orbitrap analysis of the generated peptides yielded the best data. Using these technologies I was able to investigate the relative abundance of proteins secreted into the serum of 17 controls and 53 patients with CRC. This study identified 12 potential proteins from iTRAQ analysis and 10 from from the label free platform, that were either up or down regulated in the serum of patients with CRC compared to controls
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