The Study Of COX-2 And Survivin Expression In Hepatic Cell Carcinoma(HCC) And It's Relationship With Vasoformation Of HCC

Hepatic cell carcinoma(HCC) is one of malignant tumour which prevalence rate and mortality rate are very high in the world. Compared with other country, the mortality rate of HCC is highest in our country.The therapeutic efficacy of HCC were not good for its easy to invasion transfer in the earlier period,higher recurrence rate and damage normal tissue during radiotherapy and chems.At present,the diagnose of HCC were mainly depended on imageology and AFP. But there are many difficults when identified small hepatoma and optimum noeud by imageology method such as CT,MRI et al.More than 1/3 AFP negative hepatoma should be further study.So it is our duty to find new method which can diagnosis and treat hepatoma in early period. Recently, gene diagnosis and gene treatment has been the new method of tumor diagnosis and treatment.Many scientist have studied the molecular biology base of malignant tumor to find new diagnosis marker and new treatment target,to diagnosis hepatoma in early period and increase recover rate of patients.At present,it is can be done to find new diagnosis marker and new gene treatment target following the study of the mechanism of HCC.COX is rate-limiting enzyme in the process of prostaglandin synthesized by arachidonic.It has two subtype:COX-1 and COX-2.In recently,many studies showed that COX-2 not only is key enzyme which switch on inflammatory reaction but also expressed in many human tumors.COX-2 were involved in many tumor's genesis and development by promote cell hyperplasy,inhibit apoptosis and promote new vasifaction.COX-2 has been the new hot spot because its dysexpression in many tumor.Survivin is a new member of inhibitor of aoptosis protein(IAP).It mainly expressed in developing embryonic tissue and frequently malignant tumor of human.No expression in differentiated tissue(except thymus).Its biological effects include:①inhibit apoptosis.②regulate cell propagate.③induce angiogenesis.The specificness of surviving protein expression make it to be new target of tumor diagosis and treatment.Many studies showed there are closely relationship between COX-2,surviving and the genesis,development, angiopoiesis of tumor.But the mechanism hasn't been known.If there are relationship between the expression of COX-2 and surviving,if COX-2 and surviving can be used combination have not be reported.AIM:(1)To study the expression and dependability of cyclooxyenase-2(COX-2) and survivin in HCC tissues.(2)To study the relationship between COX-2,surviving and vascular endothelial growth factor(VEGF),the effect of COX-2,surviving on angiogenesis.To supply experimental evidence for gene diagnosis and treatment of HCC.Methods:(1)Detect COX-2 and surviving in liver cancer tissue(30), latero-liver cancer tissue(20)and normal hepatic tissue(10)by flow cytometry(FCM). Analisis immunofluorescence data by CellQuestTMV3.0软件. Get data by logarithm mode, fluorescence index mean their relative amount. (2)Detect COX-2, surviving and VEGF by immunohistochemistry method (SP). At the same time, mark CD34 tumor new vessels,determine tumor microvessel density by the number of CD34 positive cells of blood vessel endothelium. Analysis the expression, dependability and the relationship with tumor neovascularization of COX-2,surviving and VEGF by SPSS software,x2 test and Spearman interclass correlation.Results: (1)Results of flow cytometry:①The expression of COX-2 in HCC(FI=1.62±0.21) were higher than in latero-liver cancer tissue(FI=0.98±0.12) and normal liver tissue(FI=1.00±0.07)(p<0.05). There are no significant differences between latero-liver cancer tissue and normal liver tissue.②The expression of surviving in HCC(FI=1.75±0.17) higher than in latero-liver cancer tissue(FI=1.21±0.12) and normal liver tissue(FI=1.00±0.07)(p<0.05). But there are no difference between latero-liver cancer tissue and normal liver tissue.③There are positive correlation between the expression of COX-2 and surviving( p<0.05).(2)Immunohistochemical results:①The positive expression rate of COX-2 in HCC,latero-liver cancer tissue and normal liver tissue are (70%,40%,0%)respective.②The positive expression rate of survivin in HCC, latero-liver cancer tissue and normal liver tissue are (76.67%,15%,0%) respective.③The positive expression rate of VEGF in HCC, latero-liver cancer tissue and normal liver tissue are (63.33%,30%,10%) respective.④There are significant positive correlation between the expression of COX-2 and surviving.⑤There are significant positive correlation between the expression of COX-2 and VEGF. There are significant positive correlation between the expression of COX-2 and MVD.⑥There are significant positive correlation between the expression of survivin and VEGF. There are significant positive correlation between the expression of suvivin and MVD.⑦There are no differences between the expression of COX-2,survivin and sex, age of patients; there are also no differences between COX-2 and size,positon,peplos,phlebocarcinoma,AFP and histodifferentiation of tumor.Conclusion: (1)The hyperexpression of COX-2 and surviving in tissue canreflex the biological behavior of HCC,and have very important role in the development of HCC.May be the new target in the gene therapy of HCC.(2) Survivin can be specificity tumor marker of liver cancer for its specific expression in HCC.(3)There are significant positive correlation between the expression of COX-2 and surviving.This means there are synergistic effect between them during the development of liver cancer.(4)There are closely relationship between survivin, COX-2 and VEGF. It means surviving and COX-2 can promote angiogenesis of tumor by VEGF, and they can co- regulate.