Expression of transforming growth factors in hepatocellular carcinoma and its relations with clinicopathological parameters and prognosis

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.

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.

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).

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.