The Clinical Effectivenesss Of VEGF,VEGFR-2 And PDGF-BB In Transcatheter Arterial Chemoembolization(TACE)and Sorafenib Of Treatment On Hepatocellular Carcinoma(HCC)

Objective:To evaluate the effect of sorafenib on transcatheter arterial chemoembolization (TACE) treated HCC patients and provide guidence for future clinical treatments through investigating the change of serum VEGF, VEGFR-2, PDGF-BB and pathological MVD, VEGF, VEGFR-2, PDGF-BB.Material and method:Partâ… TACE were applied to all 78 cases, of which 67 cases were clinical diagnosed with HCC and 11 cases were confirmed by biopsy histodiagnosis. All patients were grouped intoâ… (Stage A) andâ…¡(staget B, C and D) according to BCLC. No treatment had been applied prior to TACE. Twenty-eight patients started receiving oral sorafenib tablets 3 to 4 days after 1 or 2 TACE. In the case of positive effect, Serum VEGF, VEGFR-2, PDGF-BB level were measured with ELISA before therapy and 3 days,1 month,2 months,3 months, and 6months after therapy.Then the following studies were conducted. First, the correlation of serum VEGF, VEGF-R2, PDGF-BB level and the patients'clinical and imageology index were evaluated before and after TACE. Second, the change of serum VEGF, VEGFR-2, PDGF-BB levels were examed before and after TACE across groupâ… andâ…¡. Third, the differences of baseline values between groupâ… and groupâ…¡were investigated before the first therapy. Fourth, the contribution of serum VEGF, VEGF-R2, PDGF-BB to the developing of hepatoma was analyzed by COX proportional hazards model. Fifth, the comparision of survival rates between the oral sorafenib patients and not oral sorafenib ones also has been done. Sixth, based on long-term data, the comparison of serum VEGF, VEGF-R2, PDGF-BB levels between group that only treated with TACE and group that treated with TACE and oral sorafenib.Partâ…¡ Sixty hepatic tissue pathological sections (30 pieces of hepatoma tissue and 30 pieces of adjacent cirrhotic liver tissue) were collected in clinic. Among them,14 hepatic cellular cancer cases had done exairesis after TACE,2 cases accepted hepatectomy and liver transplantation after TACE combined with sorafenib, and 14 cases accepted simple exairesis of hepatoma tissue. Hepatoma tissue and adjacent cirrhotic liver tissue were treated with VEGF, VEGF-R2, PDGF-BB and MVD (labeled CD34) immunohistochemical staining, and simultaneously the fasting serum was colleted and ELISA test of serum VEGF, VEGF-R2 and PDGF-BB were performed.Then the following studies were conducted. First, the levels of VEGF, VEGF-R2, PDGF-BB and MVD from Hepatoma tissue and adjacent cirrhotic liver tissue were measured and compared between the pure surgery patient group and TACE+surgery patient group. The results were analyzed to show the impact of TACE. Second, between surgery only group and surgery group treated with TACE, the comparison of hepatoma tissue/ adjacent cirrhotic liver tissue factors (VEGF, VEGF-R2, PDGF-BB, and MVD) and the comparison of serum factors/ hepatoma tissue (VEGF, VEGF-R2 and PDGF-BB) were conducted. Third, a comparison analysis of serum VEGF, VEGF-R2, PDGF-BB and MVD from Hepatoma tissue and adjacent cirrhotic liver tissue was performed based on 2 cases of TACE, sorafenib and liver transplant treatment.Result:Partâ… The serum mean concentration of VEGF, VEGF-R2 and PDGF-BB of all 78 cases was 373.2 pg/ml,6082.0 pg/ml and 2289.0 pg/ml respectively before treatment. The serum index is positive when above mean concentration and negative when below mean concentration.The results of correlation analysis showed that factors that significantly positively related to the elevation of serum VEGF, VEGF-R2 and PDGF-BB includes: multiple hepatoma, tumor well-vascularized, without amicula, tumor diameter increases, tumor thrombosis in portal vein, distant metastatic, high level of hepatoma TNM grade, having survival tumor or emerging tumor. Base serum VEGF,VEGFR-2,PDGF-BB had positve correlation with prognosis.The elevation of serum VEGF and PDGF-BB is statistically significant when having remaining tumor, new tumor and tumor thrombosis in portal vein. The drop of serum VEGF and PDGF-BB is statistically significant when having good lipiodol deposit.The curves of serum VEGF and PDGF-BB of groupâ… was lower than groupâ…¡. Among them, the difference in curves of VEGF and PDGF-BB is statistically significant.Simple TACE treatment can achive good results. Comparing to TACE with sorafenib, there is no statistically significant difference. All serum VEGF,VEGFR-2 levels were higher than the mean. Most of serum PDGF-BB were higher than mean in groupâ…¡. The curve of serum VEGF and PDGF-BB of TACE with sorafenib was low and simple TACE was high and cases obtained TACE combined with sorafenib had longer survival rate in groupâ…¡.Partâ…¡Thirty cases consist of 28 cases confirmed hepatocellular carcinoma by pathological report and 2 cases receieved esection after TACE could not confirm the pathologic types because of no cancer cell found.Within the surgery only group, Hepatic cirrhosis and the expression of hepatoma tissue MVD,VEGF and VEGFR-2 had significant correlation. The serum VEGF,VEGFR-2,PDGF-BB had positive correlation with hepatoma tissue VEGF,VEGFR-2,PDGF-BB.Within TACE after surgery group, the expression of VEGF, VEGF-R2 and PDGF-BB had no statistical difference with expression of hepatoma tissue MVD,VEGF and VEGFR-2. So TACE could not cause severe vessel hyperplasia.Serum VEGF,VEGFR-2,PDGF-BB had positive correlation with hepatoma tissue VEGF,VEGFR-2,PDGF-BB in surgery only group and TACE after surgery group. Serum VEGF,VEGFR-2,PDGF-BB can be used to decide hepatoma tissue MVD,VEGF and VEGFR-2.Conclusion:1. The serum VEGF, VEGFR-2 and PDGF-BB are effective indicators for clinical effect of TACE combined with sorafenib in treatment of HCC.2. Sorafenib is not recommended when the concentration of serum VEGF, VEGFR-2 and PDGF-BB are less than 373.2 pg/ml,6082.0 pg/ml and 2289.0 pg/ml respectively, which indicates TACE is effective.3. Oral sorafenib is recommended if the concentrations are greater than above values. If the concentration levels does not come down or come down first but go back up again, then sorafenib is not effective and should not be given anymore.