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. 2 | VREEKER Et al. How to cite this article: Vreeker GCM, Hanna-Sawires RG, Mohammed Y, et al. Serum N-Glycome analysis reveals pancreatic cancer disease signatures.

Background Postpancreatectomy haemorrhage (PPH) and venous thromboembolism (VTE) are serious complications following pancreatic surgery. The aim was to assess the timing, occurrence and predictors of PPH and VTE. Methods Elective pancreatic resections undertaken in a single university hospital between November 2013 and September 2017 were assessed. Three intervals were reviewed, each with a different routine regimen of nadroparin: 2850 units once daily (single dose) administered in hospital only, or 5700 units once daily (double dose) or 2850 units twice daily (split dose) administered in hospital and continued for 6 weeks after surgery. Clinically relevant PPH (CR‐PPH) was classified according to International Study Group of Pancreatic Surgery criteria. VTE was defined according to a number of key diagnostic criteria within 6 weeks of surgery. Cox regression analyses were performed to test the hypotheses that the double‐dose group would experience more PPH than the other two groups, the single‐dose group would experience more VTE than the other two groups, and the split‐dose group would experience the fewest adverse events (PPH or VTE). Results In total, 240 patients were included, 80 per group. The double‐dose group experienced significantly more CR‐PPH (hazard ratio (HR) 2·14, 95 per cent c.i. 1·16 to 3·94; P = 0·015). More relaparotomies due to CR‐PPH were performed in the double‐dose group (16 versus 3·8 per cent; P = 0·002). The single‐dose group did not experience more VTE (HR 1·41, 0·43 to 4·62; P = 0·570). The split dose was not associated with fewer adverse events (HR 0·77, 0·41 to 1·46; P = 0·422). Double‐dose low molecular weight heparin (LMWH), high BMI and pancreatic fistula were independent predictors of CR‐PPH. Conclusion A double dose of LMWH prophylaxis continued for 6 weeks after pancreatic resection was associated with a twofold higher rate of CR‐PPH, resulting in four times more relaparotomies. Patients receiving a single daily dose of LMWH in hospital only did not experience a higher rate of VTE.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.

No abstract