Background: Transforming growth factors (TGF)-beta1, TGF-betaR2 and Smad4 belong to the TGF family, and play important roles in carcinogenesis and the development of carcinoma, especially hepatocellular carcinoma (HCC). TGF-beta1 is a multipotent polypeptide, which inhibits the growth of epithelial cells including hepatoma cell lines and hepatocytes by inducing apoptosis. TGF-betaR2 forms a heterodimeric complex upon binding to TGF-beta, and then generates the first step in the signal transduction pathway leading to growth inhibition in coordination with the type 1 receptor. Smad4 protein is an important mediator in the TGF-beta signaling pathway, and negatively regulates the growth of epithelial cells. This study aimed to detect the expression of TGF-beta1, TGF-betaR2 and Smad4 in HCCs and their adjacent normal tissues, while assessing its relations with the clinicopathological parameters of HCC.
Methods: Forty-seven HCC specimens and their adjacent normal tissues were obtained surgically at the Affiliated Hospital of Medical College, Qingdao University. The expression of TGF-beta1, TGF-betaR2 and Smad4 was separately detected by immunohistochemistry in all HCC specimens and their adjacent normal tissues, and its relations with the clinicopathological parameters of HCC were assessed.
Results: The positive expression of TGF-beta1 was 72.34% in the HCC specimens, which was higher than that in the adjacent normal tissues (P<0.001). The positive expression of Smad4 and TGF-betaR2 was 34.04% and 59.57% respectively in the carcinoma specimens. The expression of TGF-beta1, TGF-betaR2 and Smad4 was significantly higher in groups with a tumor embolus of the portal vein, integrity of the amicula, and Edmondson's III-IV than that in other groups, but it was not related to tumor size (P<0.05).
Conclusions: TGF-beta1 may play an important role in the occurrence and development of HCC. Combined detection of TGF-beta1, TGF-betaR2 and Smad4 may be useful for the determination of the degree of malignancy and the prognosis of HCC.