Are growth factors implicated in hepatocarcinogenesis: a comparative study of serum levels of transforming growth factor-alpha and insulin growth factor - II in patients with cirrhosis and hepatocellular carcinoma

ABSTRACT

Transforming growth factor - alpha [TGF-alpha] and insulin -growth factor - II [IGF-II] are important autocrine growth factors of hepatocytes. They are potent stimulators of cell. proliferation in the liver and in liver tumors. TGF-alpha and IGF-Il are over expressed in hepatic malignant tissues, and elevated serum levels can be indicator of tumor activity in addition to conventional tumor markers. Our aim was to evaluate the role of TGF-alpha together with IGF-Il in the diagnostic work - up of patients with heptocellular carcinoma [HCC]. Thirty patients with liver cirrhosis [LC], 30 with hepatocellular carcinoma [HCC] and 24 normal controls [C] were enrolled in this study- Serum TGF-alpha and IGF-II levels were measured by enzyme - linked immunosorbent assay. TGF-alpha and IGF-II serum levels were significantly elevated in cirrhotic patients [P<0.05 as compared to control] and over expressed significantly in HCC patients [P<0.001 in comparison with both cirrhotic and control groups]. Both parameters showed positive correlation in the cirrhotic group [P<0.001, r=0.886], while in the HCC group TGF-alpha and IGF-Il showed positive correlation with each other [P<0.001, r = 0.908] and also with alpha-fetoprotein [AFP] [P< 0.001, r = 0.884 and P<0.001, r =0.881 respectively]. Child C class showed the highest levels of TGF-alpha and IGF-Il in both cirrhotic and HCC groups. All patients showed HBs Ag and /or HCVAb positivity in their serum. Hepatitis B and C viruses infection is closely related with hepatocarcinogenesis. The over expression of TGF-alpha and IGF-Il in the liver and serum seem tobe associated with the regeneration of hepatocytes injured by HBsAg or/and HCV. The continued expression of TGF-alpha and IGF-II might lead to dysplasia of liver cells and development of HCC- Therefore, in addition to AFP; TGF-alpha and IGF-Il appear to be suitable markers for the evaluation of the serological status of HCC patients