Relationship And Significance Of C-MET And COX-2 Expressed In Human Hepatocellular Carcinoma

Background: Hepatocellular carcinoma is considered to be one of the most common gastric tumor and also difficult for radical cure due to advanced stage when discovered ,insensitivity to radiotherapy and chemotherapy and recurrence even after liver transplantation ,so that it is a hotpoint to explore a good specific and effective way to do with HCC. Generally speaking,considering that neovascularization provides supply for the growth of tumor,as tumor develops to a certain extent,so it may affect the prognosis to cut the supply.Therefore,more attention's paid to the strategy of angiogenesis-inhibiting therapy.On one hand,c-MET could up-regulate COX-2. HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway and phosphorylation of c-MET[1].MVD in c-MET-positive tissue of gastric cancer is higher than in c-MET-negative tissue, indicating that c-MET plays an important part in neovascularization of tumor, which affects the growth and metastasis of tumor[2]. What's more, inhibition of c-MET by NK4 ,a specific inhibitor of c-MET,defers the growth and down-regulates MVD of tumor, indicating that c-MET plays a great role in angiogenesis of tumor[3]. On the other hand, inhibition of COX-2 results in down-regulation of c-MET. Neoadjuvant selective COX-2 inhibition down-regulates expression of c-MET in patients with esophageal adenocarcinoma[4].more-over, a report of hepatic-virus-B related HCC indicates that COX-2 up-regulates expression of VEGF,perhaps through synthesis of PG[5].Above all, c-MET correlates with COX-2,which plays a significant part in angiogenesis of tumor.However,whether relationship between COX-2 and c-MET is the same in HCC remains controversery home and abroad.Therefore,to study the relationship between c- MET and COX-2 expressed in hepatocellular carcinoma as well as its significance, mean optical density of 28 slides of hepatocellular carcinoma tissue stained by immunohistochmemical method was detected with professional photo analysis system-Simple PCI 6 from Cimpix INC.USA. Main results are as follows:(1) Mean optical density of c-MET and COX-2 in hepatocellular carcinoma with hepatic cirrhosis is higher than without liver cirrhosis.(2) Mean optical density of c-MET and COX-2 is higher in hepatocellular carcinoma larger than 5cm than that smaller than 5 cm.(3) c-MET and COX-2 is positively correlated.Above all,c-MET and COX-2 may highly correlated in hepatocellular carcinoma, especially perhaps in angiogenesis of hepatocellular carcinoma.It is concluded that COX-2 may be a downstream factor of c-MET. HGF-c-MET-COX-2-VEGF may be a potential pathway, which plays a great role in angiogenesis in hepatocellular carcinoma with the size of larger than 2cm and hepatic-virus-B related.