Mapping the biomolecular deregulation in colorectal cancer using LC-MS/MS-based N-glycomics and proteomics: a quest for potential biomarkers

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. It follows a gradual progression from small polyps to early and late metastatic stages where it spreads to distant organs. There is an urgent need to develop reliable markers for the early detection of CRC when treatment options are more effective. To meet this need, an increased molecular understanding of the CRC pathology is warranted to gain insight into the underlying molecular and cellular mechanisms of the disease. The work described in this Ph.D. thesis build on a proteogenomic precursor study performed inhouse of three phenotypically and pathologically different CRC-relevant human cell lines (LIM1215, LIM1899 and LIM2405) from where a number of putatively N-glycosylated and cancer associated proteins were identified. This thesis aimed to further expand the knowledge of the biomolecular signatures associated of CRC by mapping, at the highest possible molecular resolution, the system-wide deregulation of the proteome and the protein N-glycome associated with the disease. Importantly, this structural investigation was undertaken both in vitro and in vivo using modern LC-MS/MS technologies and pathologically relevant and well-studied (LIM) cell lines and clinically relevant tissue specimen. Protein N-glycosylation was of particular interest since it a known regulator of malignant processes and an important molecular hallmark of cancer.