Dataset Information

Identification and Validation of Atypical N-Glycosylation Sites.

ABSTRACT: It is well-known that N-linked glycans usually attach to asparagine residues in the N-X-S/T motifs of proteins. However, accumulating evidence indicates that N-glycosylation could also possibly occur at other atypical motifs. In this study, we tried to identify atypical N-glycosylation sites using our recently developed solid-phase extraction of the N-linked Glycans And Glycosite-containing peptides (NGAG) method. Peptides with deamidation sites at asparagine residues but lacking a typical asparagine-X-serine/threonine sequons (N-X-S/T, X is any amino acid except proline) motif were identified from deglycosylated peptide data as potentially atypical glycosite-containing peptides. These atypical glycosites were verified by the presence of glycans on their intact glycopeptides and further confirmed by specific inhibition of cells with an N-linked glycosylation inhibitor, tunicamycin. From this study, two atypical N-linked glycosylation sites with N-X-C and N-X-V motifs were identified and validated from an ovarian cancer cell line (OVCAR-3).

SUBMITTER: Sun S

PROVIDER: S-EPMC4721579 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Identification and Validation of Atypical N-Glycosylation Sites.

Sun Shisheng S Zhang Hui H

Analytical chemistry 20151124 24

It is well-known that N-linked glycans usually attach to asparagine residues in the N-X-S/T motifs of proteins. However, accumulating evidence indicates that N-glycosylation could also possibly occur at other atypical motifs. In this study, we tried to identify atypical N-glycosylation sites using our recently developed solid-phase extraction of the N-linked Glycans And Glycosite-containing peptides (NGAG) method. Peptides with deamidation sites at asparagine residues but lacking a typical aspar ...[more]

PMID: 26593774

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Project description:IntroductionAltered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC.MethodsIn total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was composed by a stepwise ordinal logistic model in the discovery population. The receiver operating characteristic (ROC) curve with the bootstrapping procedure was used to assess the performance of the glycan score.ResultsIn the discovery population, the adjusted OR of GP20 (digalactosylated monosialylated biantennary with core and antennary fucose), IGP33 (the ratio of all fucosylated monosyalilated and disialylated structures), IGP44 (the proportion of high mannose glycan structures in total neutral IgG glycans), IGP58 (the percentage of all fucosylated structures in total neutral IgG glycans), IGP75 (the incidence of bisecting GlcNAc in all fucosylated digalactosylated structures in total neutral IgG glycans), and the glycan score are 4.03 (95% CI: 3.03-5.36, P<0.001), 0.69 (95% CI: 0.55-0.87, P<0.001), 0.56 (95% CI: 0.45-0.69, P<0.001), 0.52 (95% CI: 0.41-0.65, P<0.001), 7.17 (95% CI: 4.77-10.79, P<0.001), and 2.86 (95% CI: 2.33-3.53, P<0.001), respectively. Individuals in the highest tertile of the glycan score own an increased risk (OR: 11.41), compared with those in the lowest. The average multi-class AUC are 0.822 (95% CI: 0.786-0.849). Findings are verified in the validation population, with an average AUC of 0.807 (95% CI: 0.758-0.864).DiscussionOur study demonstrated that IgG N-glycans and the proposed glycan score appear to be promising predictive markers for ESCC, contributing to the early prevention of esophageal cancer. From the perspective of biological mechanism, IgG fucosylation and mannosylation might involve in the carcinogenesis progression of ESCC, and provide potential therapeutic targets for personalized interventions of cancer progression.

Dataset Information

Identification and Validation of Atypical N-Glycosylation Sites.

Publications

Identification and Validation of Atypical N-Glycosylation Sites.

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