The clinicopathological significance of transforming growth factor-β1, transforming growth factor-β1 receptor II ,Smad4 and Smad7

Abstract

Objective To investigate the clinicopathological significance of transforming growth factor-β1 (TGF-β1), transforming growth factor-β1 receptor Ⅱ (TGF-βRⅡ ), Smad4 and Smad7 protein expressions in gastric carcinomas. Methods 109 cases of gastric carcinomas,28 of high grade dysplasia,20 of low grade dysplasia,30 of chronic atrophic gastritis,29 of intestinal metaplasia, and 21 of normal gastric mucosa were selected for the detection of the expression level of TGF-β1,TGF-βRⅡ , Smad4 and Smad7 proteins by immunohistochemistry. Results The expression of TGF-β1,TGF-βRⅡ and Smad7 proteins in gastric carcinomas and dysplasia (high and low grade) were significantly higher than those in chronic atrophic gastritis, intestinal metaplasia and normal gastric mucosa (all P <0. 001 ) ,whereas the expression of Smad4 was significantly increased in high and low grade dysplasia (cytoplas-mic IS :4.89±2.38,5.80±1.54, respectively; nuclear IS: 3.89± 1.52,3.80±1.33, respectively), and decreased in gastric carcinomas (cytoplasmic IS:2.41±2.27,nuclear IS:2.02±2. 14) (P <0.001 ,P <0.001 ,respective-ly). Meanwhile,the expressions of TGF-β1,TGF-βRⅡ and Smad7 were higher in advanced gastric cancer (4.36± 2.66,3.05±1.93,4.84±3.06, respectively) than those in early gastric cancer ( 2.93±1.85,2. 17±1.87, 4. 14±2.46, respectively) ( P < 0.01, P < 0.05, P < 0. 05, respectively ) ; however the expression of Smad4 protein was much higher in early gastric cancer (P < 0. 001 ). The expression of Smad4 protein was significantly correlated with tumor size( P < 0.05 ), lymph node metastasis ( P < 0. 001 ), T stage ( P < 0. 001 ) and chnical stage ( P < 0.001) ,and the expressions of TGF-βRⅡ and Smad4 proteins were correlated with patients' 5-year survival rate (P<0.05 ,P < 0.01 ). TGF-β1 showed the positive correlation with TGF-βRⅡ and Smad7 (r1= 0.45 ,P <0. 05; r2 = 0.49, P <0. 05), but negative correlation with Smad4 ( r = - 0.21,P < 0.05 ). Conclusion TGF-β1, TGF-βR Ⅱ, Smad4 and Smad7 protein may play an important role in the carcinogenesis of gastric carcinoma,and smad4 is the key in TGF-β pathway. Also, the detection of these proteins expression can be a useful marker for predicting the gas-tile cancer invasion,metastasis and patients' prognosis. Key words: Gastric carcinoma; Transforming growth factor-β1; Transforming growth factor-β1 receptor; Smad4 ; Smad7