Serum N-glycome alterations in colorectal cancer associate with survival

Proteins are routinely measured in clinical laboratories for diagnosis, prognosis and therapy monitoring. Nevertheless, both test improvements (performance) and innovations (biomarkers) are needed, and protein N-glycosylation offers a rich source of potential markers. Here, we have analyzed the total serum N-glycome in a matched case-control study (124 cases versus 124 controls) of colorectal cancer patients. The results were validated in an independent sample cohort (both 61 cases versus 61 controls) and further tested in post-operative samples of cured patients. Our results revealed significant differences between patients and controls, with increased size (antennae) and sialylation of the N-glycans in the colorectal cancer patient sera as compared to mainly di-antennary N-glycans in sera from controls. Furthermore, glycan alterations showed strong associations with cancer stage and survival: The five-year survival rate largely varied between patients with an altered serum N-glycome (46%) and an N-glycome similar to controls (87%). Importantly, the total serum N-glycome showed prognostic value beyond age and stage. This clinical glycomics study provides novel serum biomarker candidates and shows the potential of total serum N-glycans as a prognostic panel. Moreover, serum N-glycome changes reverted to a control-like profile after successful treatment as was demonstrated from pre- and post-operative samples.