Expressions Of VEGFR-2、PDGFR-β、c-METand FGFR In Hepatocellular Carcinoma And Their Relationship With Prognosis

Objective:To explore the clinical significance and prognostic values of VEGFR-2, PDGFR-β, c-MET and FGFR1in patients with hepatocellular carcinoma(HCC), and search for markers that can predict sorafenib efficacy.Methods:Pathological specimens and clinical data of93HCC patients who under a therapy in the Department of Digestive oncology,307Hospital of PLA between January2007and October2011were collected, among them,65patients took sorafenib. The expression of VEGFR-2, PDGFR-β, c-MET and FGFR1in HCC-tissue was examined by the immunohistochemical method (IHC). Applied the SPSS18.0Software Package for statistical analysis. The correlation analysis between the expression of VEGFR-2, PDGFR-β, c-MET and FGFR1and Clinicopathological Features was carried out with the χ2test (or Fisher’s exact test). Analysis of influence of HCC clinicopathological features and the expression of VEGFR-2, PDGFR-β, c-MET and FGFR1on Prognosis(PFS/OS), the survival rate adopted the Kaplan-Meier survival curve, and the univariate survival analysis adopted the Log rank test, while the multivariate survival analysis adopted the Cox proportional hazard model.Results:1. Analysis of Influence of HCC Clinicopathological Features on Prognosis:The median PFS and OS of65HCC patients were4.97months and8.07months respectively. The age was related to the PFS(P<0.05), while the AFP level, tumor size, absence or presence of ascites, and absence or presence of tumor thrombus were related to the OS(P<0.05).2. Expression of VEGFR-2, PDGFR-β and c-MET in HCC:The over-expression rates of VEGFR-2,PDGFR-β,c-MET and FGFR1in93HCC patients were86%,19.4%,80.6%and35.5%, respectively.3. Relationship between expression of VEGFR-2, PDGFR-β and c-MET and clinicopathological Features.1) There was no significant relationship between VEGFR-2expression and age, AFP, tumor number, size, Child-Pugh classification, BCLC staging, ascites, tumor thrombus, extrahepatic metastasis, etc(P>0.05). but was related to the gender, HBsAg status, differentiation degree, liver cirrhosis and so on(p <0.05).2) There was no significant relationship between PDGFR-β expression and gender, age, hBsAg status, tumor size, differentiation degree, Child-Pugh classification, BCLC staging, ascites, tumor thrombus, and extrahepatic metastasis, etc(P>0.05). but was related to the AFP, tumor number, and liver cirrhosis and so on(P <0.05).3) There was no significant relationship between FGFR1expression and gender, age, HBsAg status, AFP,tumor size, differentiation degree, Child-Pugh classification, BCLC staging, liver cirrhosis, ascites and extrahepatic metastasis, etc(P>0.05). but was related to the tumor number and tumor thrombus, and so on(P <0.05).4) There was no statistically significant correlation between c-MET expression and the clinical and pathological features.4. Expression of VEGFR-2, PDGFR-β, c-MET and FGFR1and prognostic analysis of HCC patients that take sorafenib:There was no significantly statistical relationship between the level of VEGFR-2expression and progress-free survival and overall survival (P>0.05). There was no significantly statistical relationship between the level of PDGFR-β expression and progress-free survival(P>0.05), but was related to the overall survival(P=0.046). The expression of c-MET and FGFR1were related with progress-free survival(P<0.05),but were no significantly statistical relationship with overall survival(P>0.05).Conclusion:1. The age, the level of AFP, the size of tumour, whether there were ascites and cancer embolus were related with HCC prognosis.2. The high expression of VEGFR-2in patients with HCC merging the positive HBsAg and liver cirrhosis provides a new approach for understanding the occurrence, development mechanism and treatment of liver cirrhosis.3. The high expression of PDGFR-β and FGFR1were poor HCC prognosis indicator.4. C-MET might be a prognostic factor to predict the therapeutic effect of HCC patients who have taken sorafenib.