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. 2016 May 1:456:24-30.
doi: 10.1016/j.cca.2016.02.018. Epub 2016 Mar 1.

Blood expression of matrix metalloproteinases 8 and 9 and of their inducers S100A8 and S100A9 supports diagnosis and prognosis of PDAC-associated diabetes mellitus

Stefania Moz  1 , Daniela Basso  2 , Andrea Padoan  1 , Dania Bozzato  1 , Paola Fogar  3 , Carlo-Federico Zambon  1 , Michela Pelloso  1 , Cosimo Sperti  4 , Saula Vigili de Kreutzenberg  1 , Claudio Pasquali  4 , Sergio Pedrazzoli  5 , Angelo Avogaro  1 , Mario Plebani  6
Affiliations

Blood expression of matrix metalloproteinases 8 and 9 and of their inducers S100A8 and S100A9 supports diagnosis and prognosis of PDAC-associated diabetes mellitus

Stefania Moz et al. Clin Chim Acta. .

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.

Keywords: Biliary tract cancer; Matrix metalloproteinases; Pancreatic cancer; S100 proteins; Type 2 diabetes mellitus.

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