Expression Of Notch1-4 And Jagged1in Human Hepatocellular Carcinoma

Objective: Notch signaling pathway is an evolutionarily highly conserv- ed mechanism for cell-cell communication,which controls cell proliferation, differentiation,apoptosis,and plays an important role in embryogenesis and many types of cell fate determination.Notch signaling pathway has different function in different tissue cells and has different function at distinct stages of the same tissue cells.The biological function of this pathway is critically context dependent.Reports had showed that Notch signaling pathway is not only involved in the development of normal cells but also in cancer cells.Until now,the role of Notch signaling in HCC and its underlying mechanism are still unknown.To investigate the expression of Notch1-4 and Jagged1 in human hepatocellular carcinoma(HCC),adjacent non-cancerous cirrhotic hepatic tissue and normal hepatic tissue,we analyzed the association of their expression with clinicopathological parameters and the correlation among Notch1-4 and Jagged1.Methods: 1 Samples collection follow up: 50 specimens of HCC,50 specimens of adjacent non-cancerous cirrhotic hepatic tissue and 12 specimens of normal hepatic tissue were obtained from the fourth hospital of Hebei Medical University,which were not treated before operation.2 Imunostaining:The samples were fixed by 10% formaldehyde,embeded in paraffin after excision.Immunohistchemical staining was used to measure Notch1-4 and Jagged1 in HCC tissues and adjacent non-cancerous cirrhotic hepatic tissues and normal hepatic tissues,the differences of clinicopathologi- cal groups for Immunohistochemical staining were analyzed by statistical methods.Resluts: 1 Notch1 was expressed in HCC tissues,adjacent non-cancer- ous cirrhotic hepatic tissues,and normal hepatic tissues,which mostly expressed in cytoplasm.Notch1 expression in HCC tissue was much stronger than that in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue (Z=-4.004,P=0.000 and Z=-3.355,P=0.001),There was no statistical difference existed between in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue.Notch1 expression was significant stronger in better differentiation than that in poorer differentiation of HCC tissues (χ~2=6.938,P=0.031,r=-0.376,P=0.007).Notch1 expression in HCC tissues had showed no difference in different clinical stage.The Notch1 expression had no difference refered to sex,age,the number of tumor foci,size of tumor,AFP,HBsAg,HBeAg,the integrity of the tumor's envelope and the portal vein tumor thrombosis in HCC tissues based on our statistical analysis.2 Notch2 was expressed in HCC tissues,adjacent non-cancerous cirrhotic hepatic tissues and normal hepatic tissues,which mostly expressed in cytoplasm.Notch2 expression had no statistical difference among HCC tissue,adjacent non-cancerous cirrhotic hepatic tissue and normal hepatic tissue.The Notch2 expression had no difference refered to sex,age,the number of tumor foci,size of tumor,AFP,HBsAg,HBeAg,the integrity of the tumor's envelope,the portal vein tumor thrombosis,clinical stage,the pathological classification in HCC based on our statistical analysis.3 Notch3 was expressed in HCC tissues,adjacent non-cancerous cirrhotic hepatic tissues and normal hepatic tissues,which mostly expressed in cytoplasm.Notch3 expression in HCC tissue was much stronger than that in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue (Z=-2.551,P=0.011and Z=-2.436, P=0.015),There was no statistical difference existed between in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue.Notch3 expression was significant stronger in later clinical stage of HCC than earlier stage of HCC(χ~2=10.872,P=0.028,r=0.359, P=0.010), Notch3 expression showed no difference in different pathological classification of HCC. The Notch3 expression had no difference refered to sex,age,the number of tumor foci,size of tumor,AFP,HBsAg,HBeAg,the integrity of the tumor's envelope and the portal vein tumor thrombosis in HCC based on our statistical analysis.4 Notch4 was expressed in HCC tissues,adjacent non-cancerous cirrhotic hepatic tissues and normal hepatic tissues,which mostly expressed in cytoplasm.Notch4 expression in HCC tissue was much stronger than that in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue (Z=-2.906,P=0.004 and Z=-2.985,P=0.003),There was no statistical difference existed between in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue.The Notch4 expression had no difference refered to sex,age,the number of tumor foci,size of tumor,AFP,HBsAg,HBeAg,the integrity of the tumor's envelope,the portal vein tumor thrombosis,clinical stage,the pathological classification in HCC based on our statistical analysis.5 Jagged1 was expressed in HCC tissues,adjacent non-cancerous cirrhotic hepatic tissues and normal hepatic tissues,which mostly expressed in cytoplasm.Jagged1 expression in HCC tissue was much stronger than that in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue (Z=-2.747,P=0.006 and Z=-2.249,P=0.025),There was no statistical difference existed between in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue.The Jagged1 expression had no difference refered to sex,age,the number of tumor foci,size of tumor,AFP,HBsAg,HBeAg,the integrity of the tumor's envelope,the portal vein tumor thrombosis,clinical stage,the pathological classification in HCC based on our statistical analysis.6 The correlation between Notch1,Notch2,Notch3,Notch4 and Jagged1 expression in HCC:Notch1 expression had no correlation with Notch2 expression level in HCC (r=-0.003,P=0.981),Notch1 expression level had no correlation with notch3 expression in HCC (r=0.166,P=0.249),Notch1 expression had no correlation with Notch4 expression level in HCC (r=0.184, P=0.200),Notch1 expression had no correlation with Jagged1 expression in HCC(r=-0.248,P=0.082),Noth2 expression had no correlation with Notch3 expression in HCC (r=-0.054, P=0.709),Notch2 expression had no correlation with Notch4 expression in HCC (r=0.137,P=0.344),Notch2 expression had no correlation with Jagged1 expression in HCC (r=0.144, P=0.317),Noth3 expressional level had no correlation with Notch4 expression in HCC (r=0.138,P=0.339),Noth3 expression had no correlation with Jagged1 expression in HCC (r=0.166,=0.249),Nothc4 expression had no correlation with Jagged1 expression in HCC (r=0.245,P=0.086).Conclusions: 1 Notch1,Notch3,Notch4 and Jagged1 expression level in HCC tissue was much higher than that in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue,but had no statistical difference existed between in adjacent non-cancerous cirrhotic hepatic tissue and in normal hepatic tissue.2 Notch1 expression level was significantly higher in better differentiation than poorer differentiation of HCC tissues,Notch3 expression level was significantly higher in later clinical stage of HCC than earlier stage,which showed that the abnormal activition of Notch signaling pathway might take effects on the progress of HCC.