Specific glycoforms of MUC5AC and endorepellin accurately distinguish mucinous from nonmucinous pancreatic cysts

Zheng Cao, Kevin Maupin, Bryan Curnutte, Brian Fallon, Christa L. Feasley, Elizabeth Brouhard, Richard Kwon, Christopher M. West, John Cunningham, Randall Brand, Paola Castelli, Stefano Crippa, Ziding Feng, Peter Allen, Diane M. Simeone, Brian B. Haab

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2724-2734
Number of pages11
JournalMolecular and Cellular Proteomics
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

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    Cao, Z., Maupin, K., Curnutte, B., Fallon, B., Feasley, C. L., Brouhard, E., Kwon, R., West, C. M., Cunningham, J., Brand, R., Castelli, P., Crippa, S., Feng, Z., Allen, P., Simeone, D. M., & Haab, B. B. (2013). Specific glycoforms of MUC5AC and endorepellin accurately distinguish mucinous from nonmucinous pancreatic cysts. Molecular and Cellular Proteomics, 12(10), 2724-2734. https://doi.org/10.1074/mcp.M113.030700