肝细胞癌
医学
MAPK/ERK通路
蛋白激酶B
癌症研究
肝硬化
肝移植
癌症
免疫组织化学
六氯环己烷
内科学
肿瘤科
激酶
病理
细胞凋亡
移植
生物
生物化学
细胞生物学
作者
Klaus Schmitz,Jeremias Wohlschlaeger,Hauke Lang,Georgios C. Sotiropoulos,Massimo Malagó,Karen Steveling,Henning Reis,Vito R. Cicinnati,Kurt Werner Schmid,Hideo A. Baba
标识
DOI:10.1016/j.jhep.2007.08.018
摘要
The aim of the study was to determine the prognostic relevance of AKT and extracellular regulated kinases (ERK1/2), which are implied in the regulation of cell proliferation and apoptosis, in hepatocellular carcinoma (HCC).This study comprised a series of 208 patients incorporating HCCs treated either by surgical resection (n = 109) or liver transplantation (n = 99). Immunohistochemically demonstrated phospho-ERK1/2 (pERK1/2) and phospho-AKT (pAKT) was correlated with a series of clinico-pathologically relevant parameters (EGFR, Cyclin-D1, HCV/HBV infection, liver cirrhosis, chronic alcohol abuse), proliferative activity, and apoptosis.Activation of ERK1/2 correlated statistically with the presence of HCV infection. pERK1/2 (P < 0.001) and pAKT (P = 0.052) expression showed a significant correlation with a decreased overall survival (OS). In multivariate Cox regression analysis pERK1/2 was identified as an independent prognostic parameter in HCC (P = 0.026).Activation of ERK1/2 in HCC cancer indicates aggressive tumour behaviour and constitutes an independent prognostic factor. Furthermore our data confirm that HCV infection activates the ERK pathway and thereby might contribute to HCC carcinogenesis. Immunohistochemical determination of pERK1/2 status can thus be proposed as a promising candidate for the identification of high risk patients who may benefit from new anticancer drugs targeting the ERK-pathway.
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