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Open Access Research article

A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival

Puneet Singh1*, Radhika Srinivasan2, Jai Dev Wig1 and Bishan Das Radotra3

Author Affiliations

1 Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India

2 Department of Cytology and Gynaecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

3 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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BMC Research Notes 2011, 4:560  doi:10.1186/1756-0500-4-560

Published: 23 December 2011

Abstract

Background

Smad4 is the common mediator of the tumor suppressive functions of TGF-beta. Smad6 and Smad7 are the antagonists of the TGF-beta pathway. This study investigates the differential protein expressions of Smad4, Smad6 and Smad7 in tumor as compared to normal tissue of pancreatic ductal adenocarcinoma (PDAC) and compares them with clinicopathological parameters and patient survival.

Results

There was a significant difference in protein expressions of Smad4 (p = 0.0001), Smad6 (p = 0.0015) and Smad7 (p = 0.0005) protein in tumor as compared to paired normal samples. Loss of Smad7 expression correlated significantly with tumor size (r = 0.421, p < 0.036) and margin status (r = 0.431; p < .032). Patients with moderate to high Smad4 protein expression had a better survival (median survival = 14.600 ± 2.112 months) than patients with absent or weak Smad4 protein expression (median survival = 7.150 ± 0.662). In addition, advanced disease stage correlated significantly with poor prognosis.

Conclusion

Loss of Smad4 significantly correlated with poor survival of PDAC patients. In the cases where Smad4 is expressed, Smad6 inhibition is possibly a novel mechanism for Smad4 inactivation. Smad7 has a role in pathobiology of PDAC. Further investigation in the roles of Smad6 and Smad7 would help in the identification of novel therapeutic targets for PDAC.

Keywords:
Pancreas; pancreatic adenocarcinoma; Smad4; Smad6; Smad7; clinicopathological parameters; prognosis