Comparison of sialylated N-glycopeptide levels in serum of pancreatic cancer patients, acute pancreatitis patients, and healthy controls.
Serum protein glycosylation is known to be affected by pathological conditions, including cancer and inflammatory diseases. Pancreatic cancer patients would benefit from early diagnosis, as the disease is often detected in an advanced stage and has poor prognosis. Searching for changes in serum protein site-specific glycosylation could reveal novel glycoprotein biomarkers. We used Sambucus nigra lectin affinity chromatography to enrich α-2,6 sialylated tryptic N-glycopeptides from albumin-depleted sera of pancreatic cancer patients, acute pancreatitis patients, and healthy individuals, and compared their relative abundance using ultra performance LC-MS. Relative quantitation was done using the spectrum processing software MZmine. Identification was performed on the web-based tool GlycopeptideID, developed for in silico analysis of intact N-glycopeptides. Seventeen high-abundance serum proteins, mainly acute-phase proteins, and immunoglobulins, with total 27 N-glycosylation sites, and 62 glycoforms, were identified. Pancreatitis patient sera contained 38, and pancreatic cancer patients sera contained 13 glycoform changes with statistical significance (p < 0.05). In pancreatitis, up to tenfold changes were found in some glycoforms, and in pancreatic cancer, threefold. Analysis showed that the changes often concerned one or two, but not all, N-glycosylation sites in a specific glycoprotein. In conclusion, the analysis shows that pancreatic cancer, and acute pancreatitis are associated with changes in concentrations of intact sialylated N-glycopeptides derived from acute-phase proteins, and immunoglobulins, and that changes are site specific.
Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
Hilkka
H
Kontro
Sakari
S
Joenväärä
Caj
C
Haglund
Risto
R
Renkonen
D016022:Case-Control Studies; D006020:Glycopeptides / Q000097:blood* / Q000737:chemistry*; D006801:Humans; D019158:N-Acetylneuraminic Acid; D010190:Pancreatic Neoplasms / Q000097:blood*; D010195:Pancreatitis / Q000097:blood*
D006020:Glycopeptides; D019158:N-Acetylneuraminic Acid
Acute pancreatitis; Glycoproteomics; MS; Pancreatic cancer; Sialylation; Technology