The Role Of SIP1 And Smad4 Protein In Tumor Invasion And Metastasis Of Hepatocellular Carcinoma

【Objective】To investigate the expression of SIP1,Smad4 protein,TGF-β1 and E-cadherin in human hepatocellular carcinoma (HCC), the relationshipsbetween their expressions and the invasion and metastasis of HCC, and explore therole of SIP1 and Smad4 in tumor invasion and metastasis.【Methods】The expression of SIP1,Smad4,TGF-β1 and E-cadherin in 60specimens of HCC, 15 specimens of liver cirrhosis and 15 specimens of thenormal group were studied by situ hybridization and immunohistochemistry(SPmethod) respectively. The relationships between SIP1,Smad4,TGF-β1,E-cadherinand the invasion and metastasis of HCC were analysed. The relationships among theexpression of SIP1,Smad4,TGF-β1 and E-cadherin were also analysed.【Results】1. The expression of SIP1 in HCC (36/60,60.0%) was higher than thatof corresponding adjacent noncancerous tissues (21/60,35.0%), the expression ofSmad4 protein in HCC (39/60,65.0%) was higher than that of corresponding adjacentnoncancerous tissues (19/60,31.7%), the expression of TGF-β1 in HCC (41/60,68.3%)was higher than that of corresponding adjacent noncancerous tissues (25/60,41.7%).On the contrary, the decreasing expression of E-cadherin in HCC was 71.7%(43/60). 2.The expression level of SIP1 in HCC was positively correlated with the size of tumor(P≤0.05),the grade of Edmondaon's classification (P≤0.05) and tumor emboli inportal vein (P≤0.05), but negatively correlated with capsular integrity(P≤0.05). Theexpression level of Smad4 protein in HCC was negatively correlated with capsularintegrity(P≤0.05).The expression level of TGF-β1 in HCC was positively correlatedwith the size and number of tumor (P≤0.05). The expression level of E-cadherin inHCC was negatively correlated with the tumor emboli in portal vein (P≤0.01). 3. Theexpression level of SIP1 in HCC was positively correlated with the expression levelof TGF-β1(P ≤0.05), but negatively correlated with the expression level ofE-cadherin(P≤0.05). The expression level of Smad4 proten in HCC was positivelycorrelated with the expression level of TGF-β1(P≤0.05) and negatively correlatedwith the expression level of E-cadherin (P≤0.05). 【Conclusions】1.SIP1, TGF-β1 may promote the invasion and metastasis ofHCC. And the lose expression of E-cadherin may promote the invasion and metastasisof HCC.Smad4 take part in the course of invasion and metastasis of HCC,but its roleremains controversial. 2.It resulted in that SIP1, TGF-β1, E-cadherin would be usefulcriterion to predict the invasion and metastasis of HCC. 3. Down-reguratingexpression of E-cadherin directly or by TGF-β1/Smad pathway in HCC may be oneof mechanisms that SIP1 promotes the invasion and metastasis of HCC.