Prognostic impact of pERK in advanced hepatocellular carcinoma patients treated with sorafenib

Abstract

Sorafenib represents the standard of care targeted therapy for patients with advanced hepatocellular carcinoma (HCC). However, biomolecules that predict a patient's response to sorafenib treatment for HCC remain largely unknown. Thus, this study was designed to investigate whether phosphorylated ERK (pERK) and members of the sorafenib target or PI3K/Akt/mTOR signaling pathway predict the efficacy of sorafenib in advanced HCC patients. From December 2008 to October 2011, pathological specimens from 54 advanced HCC patients received sorafenib treatment were obtained. Clinicopathological variables, treatment response, survival and time to progression (TTP) were recorded. Immunophenotypical analysis was carried out using antibodies against pERK, phosphorylated S6K (pS6K), VEGFR2 and PTEN. The median overall survival (OS) and TTP were 14.2 and 3.4 months, respectively, and the disease control rate (DCR) was 59.3%. Better Eastern Cooperative Oncology Group Performance Status (ECOG PS) (95% CI: 3.27-4.93m vs. 1.15-2.85m, p=0.01), Child-Pugh class A score (95% CI: 3.47-4.53 vs. 1.14-2.06m, p<0.01), and higher pERK (3.34-6.66m vs. 1.33-2.67m, p=0.03) and VEGFR2 (3.49-6.52m vs. 2.15-2.73m, p=0.04) immunohistochemical staining score were associated with increased TTP by univariate analysis. The ECOG PS (p=0.022), Child-Pugh class (p=0.045) and pERK staining score (p=0.012) were found to be associated with TTP using multivariate analysis. Sorafenib treatment outcome is favorable in advanced HCC patients who received tumor resection and who have a good ECOG PS and Child-Pugh class A liver function. The pERK immunohistological staining score, ECOG PS and Child-Pugh class may be helpful in determining patients most likely to benefit from sorafenib therapy.