u-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth factor mRNA is down-regulated in human hepatocellular carcinoma

Hepatocyte growth factor/scatter factor (HGF/SF) is one of the most importa nt humoral mediators of liver regeneration, It is potentially related to mo lecular mechanisms of hepatocarcinogenesis via a paracrine system involving its cellular receptor, c-met. rn this study, the expression patterns of HG F and c-met were evidenced by multiplex RT-PCR in different specimens of hu man hepatic tissues (n = 71). A significant increase of c-met mRNA expressi on was detected in hepatitis (P = 0.001), cirrhosis (P = 0.006), and hepato cellular carcinoma (HCC) tissue (P = 0.003) compared with normal parenchyma and steatosis. HGF mRNA expression was significantly higher only in hepati tis (P = 0.01). Overexpression of c-met mRNA and under-expression of HGF mR NA were detected in the HCCs compared with the corresponding peri-tumoral t issues. Neither HGF nor c-met expression was related to age, sex, tumor sir e, grading, presence of pseudocapsula, and proliferative activity of the ma lignant hepatocytes. A significant inverse correlation was found between c- met mRNA expression level and survival (in months) of patients (P = 0.007), as previously shown for urokinase-type plasminogen activator (u-PA) mRNA ( P 0.027). In addition, c-met mRNA expression was strictly associated with u -PA mRNA revel in HCC samples (P = 0.001). These data show that a loss of b alance concerning HGF, c-met, and u-PA mRNA expression occurs during hepato carcinogenesis. Particularly, up-regulation of c-met and u-PA mRNA transcri ption appears to be coordinately regulated, and their revels of expression are inversely correlated with survival; they must therefore play an importa nt role in the development and progression of human HCC and may also be rel evant prognostic markers. (C) 2000 Wiley-Liss, Inc.