Abstract
Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL), mild chronic pancreatitis (MCP), severe chronic pancreatitis (SCP) and pancreatic ductal adenocarcinoma (PDAC) were subjected to proteomic analysis using a “label-free” comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma.
Highlights
Chronic pancreatitis, a destructive fibroinflammatory disease of the pancreas, can present with a variety of symptoms
Using IHC to identify the affected cell type in tissue sections, we found that versican is markedly increased in the ECM of severe chronic pancreatitis (SCP) and pancreatic ductal adenocarcinoma (PDAC) (Figure 8e–h) and to a lesser extent in mild chronic pancreatitis (MCP) compared to normal pancreas
The molecular events underlying the pathogenesis of chronic pancreatitis remains an area of great interest and uncertainty
Summary
A destructive fibroinflammatory disease of the pancreas, can present with a variety of symptoms. There are several causes of chronic pancreatitis, including toxic, obstructive, and inherited, but all lead to progressive scarring and loss of pancreatic function. Chronic pancreatitis presents with nonspecific symptoms which can be mild; the disease is significantly under-diagnosed. The prevalence of chronic pancreatitis appears to increase dramatically in the US and Europe during the past decade [1,2,3]. This is an increasingly common disease in the population and yet is difficult to diagnose yielding a very high cost per diagnosis ratio
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