title: Serum N-Glycome Characterization in Patients with Resectable Periampullary Adenocarcinoma.
abstract: Serum N-glycans are promising biomarkers for systemic disease states. Better understanding of the serum N-glycome of patients with resectable periampullary adenocarcinoma may identify novel prognostic markers for this disease. Serum N-glycans in 70 patients with resectable periampullary adenocarcinoma, 15 patients with benign periampullary tumor, and 129 healthy individuals were quantified using ultra performance liquid chromatography. High-sensitivity C-reactive protein (hsCRP) was analyzed for all samples using an immunoturbidimetric method. The N-glycome was compared to clinical and histopathological data, and to the acute phase response as measured by hsCRP. Whole-genome tumor tissue mRNA expression data were used for correlation and enrichment analysis to investigate underlying biological processes giving rise to changes in the serum N-glycome. Significant changes were found in the serum N-glycome of patients with periampullary adenocarcinoma (n = 70) compared to healthy individuals (n = 129). No significant differences were found between patients with benign (n = 15) and malignant periampullary tumors (n = 70). Many alterations in the N-glycome correlated with systemic acute phase response as measured by hsCRP. Enrichment analysis indicated that immunologic pathways of the cancer microenvironment correlate with specific features of the serum N-glycome. Certain glycans were associated with poor overall and disease free survival in patients with pancreatobiliary type of periampullary adenocarcinoma. Our study supports the hypothesis that certain factors secreted by the tumor affect liver and plasma cells to orchestrate the changes in the serum N-glycome observed. The serum N-glycome could potentially reflect modified phenotypes of the host and/or tumor microenvironment. The prognostic impact of the serum N-glycome should be evaluated in larger, prospective studies.
authors.forename: Julian
authors.initials: J
authors.lastname: Hamfjord
authors.affiliation: NIBRT GlycoScience Group, The National Institute for Bioprocessing Research and Training , Dublin, Ireland.
authors.forename: Radka
authors.initials: R
authors.lastname: Saldova
authors.affiliation: NIBRT GlycoScience Group, The National Institute for Bioprocessing Research and Training , Dublin, Ireland.
authors.forename: Henning
authors.initials: H
authors.lastname: Stöckmann
authors.affiliation: Department of Environmental and Health Studies, Faculty of Arts and Sciences, Telemark University College , 3800 Bo in Telemark, Norway.
authors.forename: Vandana
authors.initials: V
authors.lastname: Sandhu
authors.forename: Inger Marie
authors.initials: IM
authors.lastname: Bowitz Lothe
authors.forename: Trond
authors.initials: T
authors.lastname: Buanes
authors.forename: Ole Christian
authors.initials: OC
authors.lastname: Lingjærde
authors.forename: Knut Jørgen
authors.initials: KJ
authors.lastname: Labori
authors.affiliation: NIBRT GlycoScience Group, The National Institute for Bioprocessing Research and Training , Dublin, Ireland.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.affiliation: Department of Environmental and Health Studies, Faculty of Arts and Sciences, Telemark University College , 3800 Bo in Telemark, Norway.
authors.forename: Elin H
authors.initials: EH
authors.lastname: Kure
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011134:Polysaccharides / Q000032:analysis / Q000097:blood*; D012333:RNA, Messenger; D016019:Survival Analysis; D059016:Tumor Microenvironment
chemical_list: D011134:Polysaccharides; D012333:RNA, Messenger; D002097:C-Reactive Protein
keywords: N-glycan; acute phase response; inflammation; pancreatic cancer; pancreatitis; periampullary adenocarcinoma