Τετάρτη 2 Δεκεμβρίου 2020

Serum N‐Glycome analysis reveals pancreatic cancer disease signatures

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Serum N‐Glycome analysis reveals pancreatic cancer disease signatures

Serum protein glycosylation differences between pancreatic cancer patients and healthy individuals are discussed with regard to their potential to function as a diagnostic signature. Results were validated in an independent cohort and it was concluded that the serum N‐glycome analysis can serve as a basis for the development of a blood‐based diagnostic test for the detection of pancreatic cancer.


Abstract

Background &Aims

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with loco‐regional spread that makes the tumor surgically unresectable. Novel diagnostic tools are needed to improve detection of PDAC and increase patient survival. In this study we explore serum protein N‐glycan profiles from PDAC patients with regard to their applicability to serve as a disease biomarker panel.

Methods

Total serum N‐glycome analysis was applied to a discovery set (86 PDAC cases/84 controls) followed by independent validation (26 cases/26 controls) using in‐house collected serum specimens. Protein N‐glycan profiles were obtained using ultrahigh resolution mass spectrometry and included linkage‐specific sialic acid information. N‐glycans were relatively quantified and case‐control classification performance was evaluated based on glycosylation traits such as branching, fucosylation, and sialylation.

Results

In PDAC patients a higher level of branching (OR 6.19, P‐value 9.21 × 10−11) and (antenna)fucosylation (OR 13.27, P‐value 2.31 × 10−9) of N‐glycans was found. Furthermore, the ratio of α2,6‐ vs α2,3‐linked sialylation was higher in patients compared to healthy controls. A classification model built with three glycosylation traits was used for discovery (AUC 0.88) and independent validation (AUC 0.81), with sensitivity and specificity values of 0.85 and 0.71 for the discovery set and 0.75 and 0.72 for the validation set.

Conclusion

Serum N‐glycome analysis revealed glycosylation differences that allow classification of PDAC patients from healthy controls. It was demonstrated that glycosylation traits rather than single N‐glycan structures obtained in this clinical glycomics study can serve as a basis for further development of a blood‐based diagnostic test.

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