THE IMPORTANCE OF IMMUNOGLOBULIN G N-GLYCANS IN COLORECTAL CANCER

Session

Pharmaceutical and Natural Sciences

Description

Colorectal cancer (CRC) is a malignant neoplasm of the colon and the rectum. CRC is still associated with poor prognosis, low survival rate and usually relatively late diagnosis. Aims and objectives: This research aims to identify IgG N-glycans biomarkers with discriminative power to predict survival in patients with CRC. Specific aim: To analyse IgG N-glycans in 760 patients with CRC and 538 matching controls. Using recently developed high-throughput UPLC technology for IgG glycosylation analysis we analysed IgG glycome composition in 760 patients with CRC and 538 matching controls. Furthermore, IgG glycome composition was analysed in 39 plasma samples collected before initial diagnosis of CRC. When analysing clinical characteristics among patients and matching controls it was found that CRC associates with decrease in IgG galactosylation, IgG sialylation and increase in core-fucosylation of neutral glycans with concurrent decrease of core fucosylation of sialylated glycans. While a model based on age and sex did not show discriminative power (AUC=0.499), the addition of glycan variables into the model considerably increased the discriminative power of the model (AUC=0.755). Our findings suggest that genetic factors influencing glycome composition could be explored as risk factors for colorectal cancer. Finally, glyco-modifications might have relevance to tumour immune-surveilance and in predicting response to monoclonal antibodies. Considering the functional relevance of IgG glycosylation for both tumor immune-surveilance and clinical efficacy of therapy with monoclonal antibodies, individual variation in IgG glycosylation may turn out to be important for prediction of disease course or the choice of therapy.

Keywords:

Glycosylation, IgG, colorectal cancer (CRC).

Proceedings Editor

Edmond Hajrizi

ISBN

978-9951-550-95-6

Location

UBT Lipjan, Kosovo

Start Date

28-10-2023 8:00 AM

End Date

29-10-2023 12:00 AM

DOI

10.33107/ubt-ic.2023.117

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Oct 28th, 8:00 AM Oct 29th, 12:00 AM

THE IMPORTANCE OF IMMUNOGLOBULIN G N-GLYCANS IN COLORECTAL CANCER

UBT Lipjan, Kosovo

Colorectal cancer (CRC) is a malignant neoplasm of the colon and the rectum. CRC is still associated with poor prognosis, low survival rate and usually relatively late diagnosis. Aims and objectives: This research aims to identify IgG N-glycans biomarkers with discriminative power to predict survival in patients with CRC. Specific aim: To analyse IgG N-glycans in 760 patients with CRC and 538 matching controls. Using recently developed high-throughput UPLC technology for IgG glycosylation analysis we analysed IgG glycome composition in 760 patients with CRC and 538 matching controls. Furthermore, IgG glycome composition was analysed in 39 plasma samples collected before initial diagnosis of CRC. When analysing clinical characteristics among patients and matching controls it was found that CRC associates with decrease in IgG galactosylation, IgG sialylation and increase in core-fucosylation of neutral glycans with concurrent decrease of core fucosylation of sialylated glycans. While a model based on age and sex did not show discriminative power (AUC=0.499), the addition of glycan variables into the model considerably increased the discriminative power of the model (AUC=0.755). Our findings suggest that genetic factors influencing glycome composition could be explored as risk factors for colorectal cancer. Finally, glyco-modifications might have relevance to tumour immune-surveilance and in predicting response to monoclonal antibodies. Considering the functional relevance of IgG glycosylation for both tumor immune-surveilance and clinical efficacy of therapy with monoclonal antibodies, individual variation in IgG glycosylation may turn out to be important for prediction of disease course or the choice of therapy.