Faculty Collaboration Database

Discrimination between adenocarcinoma and normal pancreatic ductal fluid by proteomic and glycomic analysis. J Proteome Res 2014 Feb 07;13(2):395-407

Date

12/18/2013

Pubmed ID

24328148

Pubmed Central ID

PMC3946306

DOI

10.1021/pr400422g

Scopus ID

2-s2.0-84893818437 (requires institutional sign-in at Scopus site)   36 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 MS(n)-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.

Author List

Porterfield M, Zhao P, Han H, Cunningham J, Aoki K, Von Hoff DD, Demeure MJ, Pierce JM, Tiemeyer M, Wells L

Author

Kazuhiro Aoki PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Body Fluids
Carbohydrate Metabolism
Carcinoma, Pancreatic Ductal
Chromatography, Reverse-Phase
Glycomics
Humans
Pancreas
Pancreatitis-Associated Proteins
Proteome
Tandem Mass Spectrometry