Low-level expression of Smad7 correlates with lymph node metastasis and poor prognosis in patients with pancreatic cancer.
BACKGROUND
Whether Smad7 acts as a tumor proliferation promoting factor or as a metastatic suppressor in human pancreatic cancer remains unclear. This study aims to determine the prognostic value of Smad7 in patients with pancreatic adenocarcinoma.


METHODS
Surgical specimens obtained from 71 patients with pancreatic adenocarcinoma were immunohistochemically assessed for Smad7, Ki-67, MMP2, CD34, and Smad4 expression. The relationship between Smad7 expression and the clinicopathological characteristics of patients with pancreatic adenocarcinoma were also evaluated.


RESULTS
Fifty-one of 71 specimens (71.8%) were Smad7 positive and 20 specimens were Smad7 negative. Negative expression of Smad7 correlated with lymph node metastasis, liver metastasis after surgery, and a poor survival rate (P = 0.0004, 0.0044, and 0.0003, respectively). We also found an inverse correlation between the expression of Smad7 and MMP2 (P = 0.0189). Multivariate analysis revealed that Smad7 expression was an independent prognostic factor [hazard ratio (HR) 0.3902; 95% confidence interval (CI) 0.1839-0.8277; P = 0.0142]. Furthermore, in both Smad4-negative and Smad4-positive groups, survival of patients with Smad7-positive tumors was significantly better than those with Smad7-negative tumors (both P < 0.0001).


CONCLUSIONS
We conclude that low-level expression of Smad7 in pancreatic cancer is significantly associated with lymph node metastasis, high MMP2 expression, and poor prognosis.
Wang
Peng
P
Department of Hepatobiliary and Pancreatic Oncology, Cancer Hospital, Fudan University, 270 Dong An Road, Shanghai, China.
Fan
Jie
J
Chen
Zhen
Z
Meng
Zhi-Qiang
ZQ
Luo
Jian-Min
JM
Lin
Jun-Hua
JH
Zhou
Zhen-Hua
ZH
Chen
Hao
H
Wang
Kun
K
Xu
Zu-De
ZD
Liu
Lu-Ming
LM
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D051901:Smad4 Protein / Q000096:biosynthesis; D051906:Smad7 Protein / Q000096:biosynthesis*
D018952:Antigens, CD34; D019394:Ki-67 Antigen; C497796:SMAD4 protein, human; C497806:SMAD7 protein, human; D051901:Smad4 Protein; D051906:Smad7 Protein; D020778:Matrix Metalloproteinase 2