Discrimination between adenocarcinoma and normal pancreatic ductal fluid by proteomic and glycomic analysis

Mindy Porterfield, Peng Zhao, Haiyong Han, John Cunningham, Kazuhiro Aoki, Daniel D. Von Hoff, Michael J. Demeure, J. Michael Pierce, Michael Tiemeyer, Lance Wells

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Sensitive and specific biomarkers for pancreatic cancer are currently unavailable. The high mortality associated with adenocarcinoma of the pancreatic epithelium justifies the broadest possible search for new biomarkers that can facilitate early detection or monitor treatment efficacy. Protein glycosylation is altered in many cancers, leading many to propose that glycoproteomic changes may provide suitable biomarkers. In order to assess this possibility for pancreatic cancer, we have performed an in-depth LC-MS/MS analysis of the proteome and MSn-based characterization of the N-linked glycome of a small set of pancreatic ductal fluid obtained from normal, pancreatitis, intraductal papillary mucinous neoplasm (IPMN), and pancreatic adenocarcinoma patients. Our results identify a set of seven proteins that were consistently increased in cancer ductal fluid compared to normal (AMYP, PRSS1, GP2-1, CCDC132, REG1A, REG1B, and REG3A) and one protein that was consistently decreased (LIPR2). These proteins are all directly or indirectly associated with the secretory pathway in normal pancreatic cells. Validation of these changes in abundance by Western blotting revealed increased REG protein glycoform diversity in cancer. Characterization of the total N-linked glycome of normal, IPMN, and adenocarcinoma ductal fluid clustered samples into three discrete groups based on the prevalence of six dominant glycans. Within each group, the profiles of less prevalent glycans were able to distinguish normal from cancer on this small set of samples. Our results emphasize that individual variation in protein glycosylation must be considered when assessing the value of a glycoproteomic marker, but also indicate that glycosylation diversity across human subjects can be reduced to simpler clusters of individuals whose N-linked glycans share structural features.

Original languageEnglish (US)
Pages (from-to)395-407
Number of pages13
JournalJournal of Proteome Research
Volume13
Issue number2
DOIs
StatePublished - Feb 7 2014

Keywords

  • N-linked glycan
  • biomarker
  • glycomics
  • pancreatic cancer
  • proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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    Porterfield, M., Zhao, P., Han, H., Cunningham, J., Aoki, K., Von Hoff, D. D., Demeure, M. J., Pierce, J. M., Tiemeyer, M., & Wells, L. (2014). Discrimination between adenocarcinoma and normal pancreatic ductal fluid by proteomic and glycomic analysis. Journal of Proteome Research, 13(2), 395-407. https://doi.org/10.1021/pr400422g