Expression And Significance Of UPA And MMP-9 In Hepatocellular Carcinoma

Background ang Objective:Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in China.The one of biologic features of HCC is the tumore cells growing in portal vein and metastasising in the liver.HCC first invades surrounding tissue or metastasizes within the liver.Then,HCC may also metastasize to lymph node through lymphatic pathway or to other organs through hematogenous pathway in advanced stage.Invasion and metastasis are the one of the reasons of poor prognosis of HCC,and this process is related to the protease system,Urokinase plasminogen activator(uPA) system and matrix metalloproteinases(MMPs)play a important role in the process.It was proven that uPA and matrix metalloproteinases-9 (MMP-9)are the most important erzymes in degrada extracellular matrix(ECM),they also association with angiogenesis and adhesion between ceils.But the combine expression of these two molecules in HCC,their relationship with pathology and clinic are unknown.In the present study,We would like to explore the expression of uPA and MMP-9 in HCC,and their effect and significance in the development of HCC.Materials and Methods:All of the 45 surgical specimens of HCC and their adjacent liver tissues(from Dec.2004 to Apr.2006)were obtained from the department of liver and gall surgery of the first hospital affiliated to GuangXi Medical University,7 cases of adjacent liver tissues from hemangiomas of liver(as control group). Reverse transcription polymerase chain reaction(RT-PCR)and immunohistochemistry were used to detect the expression of uPA and MMP-9 in this specimens.The results were used to analyse the relationship between the expression of uPA and MMP-9 in HCC and the information of pathology and clinic(including the portal vein tumor thrombus, the presence of metastasis,hepatitis B virus,pathological stage, the level of serum alpha-fetoprotein(AFP)and the diameter of tumor).Results:1.RT-PCR was used to detect the expression of uPA in 45 cases.The positive rate of uPA mRNA in HCC was 100%(45/45),the rates of their adjacent liver tissues and the control group were 84.44%(38/45)and 28.57%(2/7)respectively(P＜0.01,P＜0.05).The positive rate of u-PA mRNA in HCC was significantly correlated with the portal vein tumor thrombus,the presence of metastasis(P＜0.01),but not correlated with the hepatitis B virus,pathological stage,the level of serum AFP and the diameter of tumor(P＞0.05)2.RT-PCR was used to detect the expression of MMP-9 in 45 cases.The positive rate of MMP-9 mRNA in HCC was 100%(45/45),the rates of their adjacent liver tissues and the control group were 86.67%(39/45)and 57.14%(4/7)respectively(P＜0.05,P＜0.01).the positive rate of MMP-9 mRNA in HCC was significantly correlated with the portal vein tumor thrombus,the presence of metastasis(P＜0.01),but not correlated with the hepatitis B virus,pathological stage,the level of serum alpha-fetoprotein(AFP)and the diameter of tumor(P＞0.05)3.Immunohistochemistry revealed that,among 45 cases,the positive rates of uPA protein were 75.56%(34/45)in HCC,26.67%(12/45) in their adjacent liver tissues,and 28.57%(2/7)in the control group, respectively(P＜0.05,P＜0.01).In addition,the positive rate of uPA protein in HCC was significantly correlated with the portal vein tumor thrombus,the.presence of metastasis(P＜0.01),but not correlated with the hepatitis B virus,pathological stage,the level of serum alpha-fetoprotein(AFP)and the diameter of tumor(P＞0.05).4.Immunohistochemistry revealed that,among 45 cases,the positive rates of MMP-9 protein were 66.67%(30/45)in HCC, 22.22%(10/45)in their adjacent liver tissues,and 14.29%(1/7)in the control group,respectively(P＜0.01,P＜0.05).In addition,the positive rate of MMP-9 protein in HCC was significantly correlated with the portal vein tumor thrombus,the presence of metastasis(P＜0.01),but not correlated with the hepatitis B virus,pathological stage,the level of serum alpha-fetoprotein(AFP)and the diameter of tumor(P＞0.05)5.By Spearman correlation analysis,the expression of uPA and MMP-9 mRNA.is positively correlation(r_s=0.749,P＜0.01),the expression of uPA and MMP-9 protein is also positively correlation(r_s =0.475,P＜0.01)Conclusions:The high level of expression of u-PA and MMP-9 in HCC might be related to the growth,invasion and metastasis of HCC,and they might be used as markers of prognosis of HCC in clinical practice.