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. 2018 Jun 5;8(1):8655.
doi: 10.1038/s41598-018-26805-7.

Plasma N-glycans in colorectal cancer risk

Margaret Doherty  1   2 , Evropi Theodoratou  3   4 , Ian Walsh  5 , Barbara Adamczyk  6   7 , Henning Stöckmann  6 , Felix Agakov  8 , Maria Timofeeva  4 , Irena Trbojević-Akmačić  9 , Frano Vučković  9 , Fergal Duffy  6 , Ciara A McManus  6 , Susan M Farrington  4 , Malcolm G Dunlop  4 , Markus Perola  10 , Gordan Lauc  9   11 , Harry Campbell  3   4 , Pauline M Rudd  6
Affiliations

Plasma N-glycans in colorectal cancer risk

Margaret Doherty et al. Sci Rep. .

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.

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Conflict of interest statement

Professor Gordan Lauc is founder and owner of Genos Ltd – a private research organization that specialises in high-throughput glycomic analysis. ITA and FV are employees of Genos Ltd.

Figures

Figure 1
Figure 1
The Oxford notation by example. Inset: the most common residues in N-glycans and their linkages. Note that linkage information may be left ambiguous e.g. F(6)A1[3] may be written FA1.
Figure 2
Figure 2
(a) A representative chromatogram from human plasma N-glycome and peak assignments from the CRC cohort. Significant peaks (found on training set of 625 patients vs. 468 control) are coloured in red (increased in CRC) and blue (decreased in CRC). ‘*’ indicates one of the top five peak abundance changes (i.e. lowest p-value). (b) Significant peaks are marked decreased (blue) or increased (red) in all CRC and four stages of CRC.
Figure 3
Figure 3
Boxplots showing increased and decreased glycan abundance for the derived glycome traits. The dots represent an individual’s relative abundance for the trait. Statistically significant traits can be found in Table 2.
Figure 4
Figure 4
Classification of CRC patients using plasma glycans. ROC curve illustrating the performance of perceptron model in discrimination between CRC patients and healthy controls from SOCCS retrospective study (625 CRC vs. 468 control). “All peaks’: 42 peak areas. ‘All peaks + clinical’: 42 peak areas, BMI, age, gender, smoking status, physical activity, NSAIDs intake, Kcalorie intake and CRP. All peaks + CRP: 42 peak areas and CRP only. ‘Clinical only’: BMI, age, gender, smoking status, physical activity, NSAIDs intake, Kcalorie intake and CRP. ‘CRP only: the only variable used is CRP’.
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