Stefania Moz1, Daniela Basso2, Andrea Padoan1, Dania Bozzato1, Paola Fogar3, Carlo-Federico Zambon1, Michela Pelloso1, Cosimo Sperti4, Saula Vigili de Kreutzenberg1, Claudio Pasquali4, Sergio Pedrazzoli5, Angelo Avogaro1, Mario Plebani6. 1. Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. 2. Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: daniela.basso@sanita.padova.it. 3. Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy. 4. Department of Surgical, Oncological and GastroenterologicalSciences - DISCOG, University of Padova, via Giustiniani 2, 35128 Padova, Italy. 5. Associazione Wirsung-onlus, via Giustiniani 2, 35128 Padova, Italy. 6. 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.
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.
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: Phil A Hart; Melena D Bellin; Dana K Andersen; David Bradley; Zobeida Cruz-Monserrate; Christopher E Forsmark; Mark O Goodarzi; Aida Habtezion; Murray Korc; Yogish C Kudva; Stephen J Pandol; Dhiraj Yadav; Suresh T Chari Journal: Lancet Gastroenterol Hepatol Date: 2016-10-12
Authors: Michal Holub; Eva Bartáková; Alžběta Stráníková; Eva Koblihová; Simona Arientová; Marie Blahutová; Jan Máca; Miroslav Ryska Journal: Mediators Inflamm Date: 2019-09-09 Impact factor: 4.711