Serum N-glycome alterations in colorectal cancer associate with survival

// Stefan W. de Vroome 1, * , Stephanie Holst 2, * , Mar Rodriguez Girondo 3 , Yuri E.M. van der Burgt 2 , Wilma E. Mesker 1 , Rob A.E.M. Tollenaar 1 and Manfred Wuhrer 2 1 Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands 2 Center for Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands 3 Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands * These authors contributed equally to this work Correspondence to: Stephanie Holst, email: s.holst@lumc.nl Keywords: N-glycans; colorectal cancer; serum biomarker panel; prognosis, survival Received: May 30, 2018 Accepted: June 25, 2018 Published: July 17, 2018 ABSTRACT 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.