title: Specific glycoforms of MUC5AC and endorepellin accurately distinguish mucinous from nonmucinous pancreatic cysts.
abstract: Specific protein glycoforms may be uniquely informative about the pathological state of a cyst and may serve as accurate biomarkers. Here we tested that hypothesis using antibody-lectin sandwich arrays in broad screens of protein glycoforms and in targeted studies of candidate markers. We profiled 16 different glycoforms of proteins captured by 72 different antibodies in cyst fluid from mucinous and nonmucinous cysts (n = 22), and we then tested a three-marker panel in 22 addition samples and 22 blinded samples. Glycan alterations were not widespread among the proteins and were mainly confined to MUC5AC and endorepellin. Specific glycoforms of these proteins, defined by reactivity with wheat germ agglutinin and a blood group H antibody, were significantly elevated in mucinous cysts, whereas the core protein levels were not significantly elevated. A three-marker panel based on these glycoforms distinguished mucinous from nonmucinous cysts with 93% accuracy (89% sensitivity, 100% specificity) in a prevalidation sample set (n = 44) and with 91% accuracy (87% sensitivity, 100% specificity) in independent, blinded samples (n = 22). Targeted lectin measurements and mass spectrometry analyses indicated that the higher wheat germ agglutinin and blood group H reactivity was due to oligosaccharides terminating in GlcNAc or N-acetyl-lactosamine with occasional α1,2-linked fucose. The results show that MUC5AC and endorepellin glycoforms may be highly specific and sensitive biomarkers for the differentiation of mucinous from nonmucinous pancreatic cysts.
authors.affiliation: Van Andel Research Institute, Grand Rapids, Michigan 49503;
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cao
authors.forename: Kevin
authors.initials: K
authors.lastname: Maupin
authors.forename: Bryan
authors.initials: B
authors.lastname: Curnutte
authors.forename: Brian
authors.initials: B
authors.lastname: Fallon
authors.forename: Christa L
authors.initials: CL
authors.lastname: Feasley
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brouhard
authors.forename: Richard
authors.initials: R
authors.lastname: Kwon
authors.forename: Christopher M
authors.initials: CM
authors.lastname: West
authors.forename: John
authors.initials: J
authors.lastname: Cunningham
authors.forename: Randall
authors.initials: R
authors.lastname: Brand
authors.forename: Paola
authors.initials: P
authors.lastname: Castelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Crippa
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: Peter
authors.initials: P
authors.lastname: Allen
authors.forename: Diane M
authors.initials: DM
authors.lastname: Simeone
authors.forename: Brian B
authors.initials: BB
authors.lastname: Haab
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D020420:Cyst Fluid; D005260:Female; D006031:Glycosylation; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism*; D010181:Pancreatic Cyst / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019812:Heparan Sulfate Proteoglycans; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D010446:Peptide Fragments; D011134:Polysaccharides; C071927:perlecan