Serum N‐Glycome analysis reveals pancreatic cancer disease signatures. (8th September 2020)

• Record Type: Journal Article
• Authors: Vreeker, Gerda C. M.; Hanna‐Sawires, Randa G.; Mohammed, Yassene; Bladergroen, Marco R.; Nicolardi, Simone; Dotz, Viktoria; Nouta, Jan; Bonsing, Bert A.; Mesker, Wilma E.; van der Burgt, Yuri E. M.; Wuhrer, Manfred; Tollenaar, Rob A. E. M.
• Is Part Of: Cancer medicine. Volume 9:Number 22(2020)
• Page Start: 8519
• Page End: 8529
• Publication Date: 2020-09-08
• Subjects: cancer biomarker analysis -- mass spectrometry‐based N‐glycan profiling -- N‐glycome analysis -- pancreatic cancer -- serum test; 616.994005
• DOI: 10.1002/cam4.3439
• Languages: English
• ISSNs: 2045-7634

Abstract

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. Abstract : 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.