Background: Early diagnosis of chronic pancreatitis by mass spectrometry-based proteomics may result in therapies to retard or modify disease progression. We aimed to identify differences in posttranslational modifications (PTMs) in pancreatic fluid proteins from individuals with chronic pancreatitis (n. = 9) and non-pancreatitis controls (n. = 9). Methods: We collected proteomic data from pancreatic fluid using mass spectrometry techniques. We performed database searches with emphasis on PTMs using ProteinPilot. We compared the frequency of specific PTMs in pancreatic fluid between cohorts and also to those identified in bile, gastroduodenal fluid, urine, and pancreatic duct and stellate cell lysates. Results: We identified 97 PTMs in endoscopically-collected pancreatic fluid, of which 11 were identified exclusively in one cohort and 9 others were significantly different in frequency between cohorts. Comparing pancreatic fluid with other specimens revealed differences in specific PTM frequencies, indicating that the identified PTMs were not merely artifacts of sample processing. Conclusions: We determined PTMs of proteins extracted from pancreatic fluid which differed in frequency in chronic pancreatitis patients verses controls. Such PTMs may serve as biomarker candidates of chronic pancreatitis upon validation with larger cohorts. The analysis of the PTM profile of pancreatic fluid proteins offers an alternative method to standard protein-based biomarker discovery. Biological significance: The early diagnosis of chronic pancreatitis is paramount in developing strategies to modify, retard, or halt disease progression. In the present study, we compared post-transitional modifications (PTMs) of proteins extracted from pancreatic fluid of chronic pancreatitis patients verses a control cohort. With many mass spectrometry-based proteomics workflows aimed to identify and quantify proteins, data for PTMs typically comes gratis, in that such data are collected during protein sequencing and, as such, require only downstream bioinformatics processing. We identified a total of 20 PTMs which were exclusive to or significantly different between cohorts. Upon validation with larger cohorts and enrichment of these PTMs may serve as biomarker candidates of chronic pancreatitis. PTM profiling of pancreatic fluid proteins is complementary to standard protein-based biomarker discovery, and may be readily applied to studies of pancreatic disease. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine.
|Number of pages||12|
|Journal||Journal of Proteomics|
|State||Published - Oct 30 2013|
Bibliographical noteFunding Information:
Funds were provided by the following NIH grants: 1F32 DK085835-01A1 (JP), 1 R21 DK081703-01A2 (DC) and 5 P30 DK034854-24 (Harvard Digestive Diseases Center; DC). We would like to thank the Burrill family for their generous support through the Burrill Research Grant. We would also like to thank members of the Steen Laboratory at Children's Hospital Boston, in particular John FK Sauld and Ali Ghoulidi for their technical assistance and critical reading of the manuscript. In addition, we thank members of the Center for Pancreatic Disease at Brigham and Women's Hospital, particularly Shadeah Suleiman for her technical assistance.
- Chronic pancreatitis
- Pancreas juice
- Pancreatic function test
ASJC Scopus subject areas