Abstract
Aberrant glycosylation has been associated with a number of diseases including cancer. Our aim was to elucidate changes in whole plasma N-glycosylation between colorectal cancer (CRC) cases and controls in one of the largest cohorts of its kind. A set of 633 CRC patients and 478 age and gender matched controls was analysed. Additionally, patients were stratified into four CRC stages. Moreover, N-glycan analysis was carried out in plasma of 40 patients collected prior to the initial diagnosis of CRC. Statistically significant differences were observed in the plasma N-glycome at all stages of CRC, this included a highly significant decrease in relation to the core fucosylated bi-antennary glycans F(6)A2G2 and F(6)A2G2S(6)1 (P < 0.0009). Stage 1 showed a unique biomarker signature compared to stages 2, 3 and 4. There were indications that at risk groups could be identified from the glycome (retrospective AUC = 0.77 and prospective AUC = 0.65). N-glycome biomarkers related to the pathogenic progress of the disease would be a considerable asset in a clinical setting and it could enable novel therapeutics to be developed to target the disease in patients at risk of progression.
Highlights
Aberrant glycosylation has been associated with a number of diseases including cancer
Total plasma N-glycan composition was determined by ultra-performance liquid chromatography (UPLC) analysis of 2AB-labelled glycans as reported for HPLC25 and more recently for UPLC where Saldova et al.12 carried out extensive glycan analysis using exoglycosidase sequencing and MS to confirm all structures and populate a database
Further evidence that at-risk groups can be identified was confirmed by using all peak areas and age of individuals in our classification algorithm showing some discrimination power to identify at risk individuals (FINRISK dataset; Table 5; Area Under the ROC Curve (AUC) 0.651). In this extensive comprehensive study, glycoforms were analysed in plasma from colorectal cancer patients and we assessed the correlation between specific glycan structures with associated CRC risk factors
Summary
Aberrant glycosylation has been associated with a number of diseases including cancer. Significant differences were observed in the plasma N-glycome at all stages of CRC, this included a highly significant decrease in relation to the core fucosylated bi-antennary glycans F(6)A2G2 and F(6)A2G2S(6) (P < 0.0009). Analysis of the glycosylation pattern in biofluids such as serum or plasma may be expected to provide useful biomarkers as the host responds to disease or as tumours secrete certain proteins8,9,. In this study a high-throughput (HTP) automated ultra-performance liquid chromatography (UPLC)-fluorescent method was used to examine the plasma N-glycome from over one thousand patients diagnosed with CRC and significant cancer associated N-glycan alterations were identified in relation to CRC risk. UPLC hydrophilic interaction liquid chromatography with fluorescence detection (HILIC) was utilized to characterise the glycosylation profile of plasma samples from 633 CRC patients and 478 matched healthy population controls. The predictive value of the relative glycan abundances to discriminate CRC from healthy control and identify at risk individuals using optimized classification algorithms was assessed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
