title: 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.
authors.affiliation: NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, United Kingdom. Electronic address: Quentin.Nunes@liverpool.ac.uk.
authors.forename: Q M
authors.initials: QM
authors.lastname: Nunes
authors.forename: V
authors.initials: V
authors.lastname: Mournetas
authors.forename: B
authors.initials: B
authors.lastname: Lane
authors.forename: R
authors.initials: R
authors.lastname: Sutton
authors.forename: D G
authors.initials: DG
authors.lastname: Fernig
authors.forename: O
authors.initials: O
authors.lastname: Vasieva
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D030541:Databases, Genetic; D005109:Extracellular Matrix / Q000378:metabolism; D053263:Gene Regulatory Networks; D006801:Humans; D010182:Pancreatic Diseases / Q000378:metabolism*; D058954:Pancreatic Stellate Cells / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism; D019512:Pancreatitis, Alcoholic / Q000378:metabolism; D050500:Pancreatitis, Chronic / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D012333:RNA, Messenger; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Bioinformatics; Heparan sulfate; Heparin; Heparin-binding protein