Expression and Prognostic Value of Small Mothers Against Decapentaplegic 7, Matrix Metalloproteinase 2, and Matrix Metalloproteinase 9 in Resectable Pancreatic Ductal Adenocarcinoma.

Abstract

Thus far, expression, clinicopathologic, and prognostic implication of small mothers against decapentaplegic 7 (Smad7), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in pancreatic ductal adenocarcinoma (PDAC) were rarely investigated or controversial. Expression of Smad7, MMP2, and MMP9 was detected using immunohistochemistry in tissue microarrays based on 322 patients with curatively resected PDAC. Their expression pattern, clinicopathologic, and prognostic relevance were further evaluated. Smad7 expression was found to be lower in tumor than in adjacent nontumor tissues, whereas tumoral MMP2 and MMP9 staining scores were much higher than in adjacent nontumor ones. Furthermore, Smad7 was negatively associated with serum carbohydrate antigen 19-9 level. Univariate survival analyses showed that patients with high Smad7 tumors had significantly better disease-specific survival (P = 0.0007), whereas MMP2 and MMP9 predicted poor disease-specific survival (P = 0.0211 and 0.0404). In multivariate Cox regression test, Smad7 was an independent prognostic indicator (P = 0.021). In addition, these 3 proteins were also prognostic in many subgroups. Smad7 and MMP2/9 significantly predict good or poor prognosis in resectable PDAC, respectively. Therefore, the genes might serve as a tool or targets for molecular therapy in PDAC.