Clinical Trial And Efficacy Prediction Of Sorafenib In Primary Hepatocellular Carcinoma

[Objective] Hepatocellular carcinoma (HCC) is the most common cancer worldwide, Some genes mutation and some growth factors have been clarified to relate to hepatocellular carcinoma, such as the overexpression of Ras、Raf、MEK、Erk and VEGF、EGFR、PDGFR-a、PDGFR-β. Ras/Raf/MEK pathway is inhibited by Sorafenib, and it maybe a prognostic factor of sorafenib. Moreover, some growth factors and their receptors may also affect the efficacy of sorafenib, such as VEGF, PDGFR, KIT. Our research is to study the expression of Ras, Raf-1, c-Kit, pMEK1/2, pERKl/2, PDGFR-a, PDGFR-β, EGFR in HCC, and evaluate the relationship between these proteins and the survival of HCC. Meanwhile, our study is to identify the biomarkers of HCC which can predict the efficacy of sorafenib.[Methods] A retrospective analysis of114patients with primary hepatocellular carcinoma who had been administered sorafenib for more than one month in our hospital from Jan2008to Dec2011. Among all the patients, we chose32cases who received surgery therapy and detected the expression of Ras, Raf-1, c-Kit, pMEK1/2, pERKl/2, PDGFR-a, PDGFR-β, EGFR in these tissue by immunohistochemistry method. To analyze the relationship between the expression of Ras, Raf-1, c-Kit, pMEKl/2, pERKl/2, PDGFR-a, PDGFR-β, EGFR and the survival of HCC[Results]1. Untill the destinaion of our study, there were70cases dead among114cases. The median overall survival (OS) was13months. The median time to progression (TTP) was7months. Patients with ECOG0, Child-Pugh A, BCLC Stage B or without extrahepatic metastasis had better prognosis. There were no correlation between the prognosis of patients and gender, age, the type of hepatitis, hepatocirrhosis, vascular involved, the level of AFP and the treatment of TACE. Cox proportional hazard regression model showed that ECOG was the significant prognostic factors of OS and TTP in HCC.2. The median OS in Ras weak-expression group were significantly longer than that in over-expression group (p=0.051). The median OS in pMEKl/2weak-expression group were significantly longer than that in over-expression group (p=0.084). The median OS in Raf-1weak-expression group was longer than that in over-expression group (p>0.05). The median OS in over-expression groups of c-Kit, pERKl/2, PDGFR-a, PDGFR-β and EGFR was longer than that in weak-expression groups (p>0.05). The median TTP in weak-expression groups of Ras, pMEKl/2and EGFR was longer than that in over-expression groups (p>0.05). The median TTP in over-expression groups of pERKl/2and PDGFR-β was longer than that in weak-expression groups (p>0.05). The weak-expression groups and the over-expression groups of Raf-1, c-Kit and PDGFR-a had the same TTP (p>0.05). The patients who got PR and SD with PDGFR-a over-expression is more than those with PDGFR-a weak-expression(p=0.075).3. Our study showed that there were significant positive correlation between the expression of pERKl/2and Raf-1、c-Kit、pMEK1/2、PDGFR-β. There were also significant positive correlation between the expression of c-Kit and PDGFR-β.[Conclusions] The patients with early ECOG, Child-Pugh A, BCLC Stage B and without extrahepatic metastasis had better prognosis. Cox proportional hazard regression model showed that ECOG status was an independent risk factor affecting the prognosis of HCC. The median OS of patients with weak-expression of Ras and pMEKl/2were longer than those in the over-expression groups, which was suggested that Ras and pMEKl/2maybe the prognostic factors of sorafenib in advanced HCC. The median TTP and OS in over-expression group of pERKl/2was longer than those in weak-expression group, which was concluded that pERKl/2maybe the important predictive biomarkers of sorafenib.