The heparin-binding protein interactome in pancreatic diseases

Abstract

Background: The cellular microenvironment plays an important role in the regulation of homoeostasis and is a source of potential biomarkers and drug targets. In a genome-wide analysis the extracellular proteins that bind to heparin (HBPs) have been shown to form highly modular and interconnected extracellular protein regulatory networks. Using a systems biology approach, we have investigated the role of HBP networks in the normal pancreas and pancreatic digestive diseases.

Methods: Lists of mRNAs encoding for HBPs associated with the normal pancreas (NP), acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) were obtained using public databases and publications. Networks of the putative protein interactomes derived from mRNA expression data of HBPs were built and analysed using cluster analysis, gene ontology term enrichment and canonical pathways analysis.

Results: The extracellular heparin-binding putative protein interactomes in the pancreas were better connected than their non heparin-binding counterparts, having higher clustering coefficients in the normal pancreas (0.273), acute pancreatitis (0.457), chronic pancreatitis (0.329) and pancreatic ductal adenocarcinoma (0.269). 'Hepatic Fibrosis/Hepatic Stellate Cell Activation' appears to be a significant canonical pathway in pancreatic homoeostasis in health and disease with a large number of important HBPs.

Conclusions: Our analyses clearly demonstrate that HBPs form disease-specific and highly connected networks that can be explored for potential biomarkers and as collective drug targets via the modification of heparin binding properties.

Keywords: Bioinformatics; Heparan sulfate; Heparin; Heparin-binding protein.