title: Blood expression of matrix metalloproteinases 8 and 9 and of their inducers S100A8 and S100A9 supports diagnosis and prognosis of PDAC-associated diabetes mellitus.
abstract: BACKGROUND
  Based on the knowledge that matrix metalloproteinases (MMPs) and S100A8/A9 synergistically work in causing PDAC-associated type 2 diabetes mellitus (T2DM), we verified whether tissue and blood MMP8, MMP9, S100A8 and S100A9 expression might help in distinguishing PDAC among diabetics.
  
  
  METHODS
  Relative quantification of MMP8, MMP9, S100A8 and S100A9 mRNA was performed in tissues obtained from 8 PDAC, 4 chronic pancreatitis (ChrPa), 4 non-PDAC tumors and in PBMCs obtained from 30 controls, 43 T2DM, 41 ChrPa, 91 PDAC and 33 pancreatic-biliary tract tumors.
  
  
  RESULTS
  T2DM was observed in PDAC (66%), in pancreatic-biliary tract tumors (64%) and in ChrPa (70%). In diabetics, with or without PDAC, MMP9 tissue expression was increased (p<0.05). Both MMPs increased in PDAC and MMP9 increased also in pancreatic-biliary tract tumors PBMCs. In diabetics, MMP9 was independently associated with PDAC (p=0.025), but failed to enhance CA 19-9 discriminant efficacy. A highly reduced S100A9 expression, found in 7 PDAC, was significantly correlated with a reduced overall survival (p=0.015).
  
  
  CONCLUSIONS
  An increased expression of tissue and blood MMP9 reflects the presence of PDAC-associated diabetes mellitus. This finding fits with the hypothesized role of MMPs as part of the complex network linking cancer to diabetes.
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Moz
authors.affiliation: Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: daniela.basso@sanita.padova.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Basso
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Padoan
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Dania
authors.initials: D
authors.lastname: Bozzato
authors.affiliation: Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fogar
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Zambon
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Pelloso
authors.affiliation: Department of Surgical, Oncological and GastroenterologicalSciences - DISCOG, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Sperti
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Saula
authors.initials: S
authors.lastname: Vigili de Kreutzenberg
authors.affiliation: Department of Surgical, Oncological and GastroenterologicalSciences - DISCOG, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pasquali
authors.affiliation: Associazione Wirsung-onlus, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Pedrazzoli
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.affiliation: Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy; Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D040501:Calgranulin A / Q000097:blood / Q000235:genetics; D040502:Calgranulin B / Q000097:blood / Q000235:genetics; D017364:Collagenases / Q000097:blood / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000097:blood / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; D012333:RNA, Messenger; D017364:Collagenases; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9
keywords: Biliary tract cancer; Matrix metalloproteinases; Pancreatic cancer; S100 proteins; Type 2 diabetes mellitus