Activation of JNK and high expression level of CD133 predict a poor response to sorafenib in hepatocellular carcinoma
British Journal of Cancer, 05/21/2012
Hagiwara S et al. – In addition, JNK activity was significantly correlated with CD133 expression level. Correspondingly, high expression level of CD133 was linked to a poor response to sorafenib. Furthermore, D-JNKi, a specific JNK inhibitor, reduced the growth of xenografted CD133+ cells in athymic mice. In conclusion, JNK activation was positively correlated with CD133 expression level and inversely correlated with the therapeutic response to sorafenib, suggesting that JNK activity may be considered as a new predictive biomarker for response to sorafenib treatment.Methods
- We collected pathological specimens from 39 patients with advanced HCC before starting sorafenib treatment, and measured JNK activity in HCCs.
- In patients treated with sorafenib, the expression of phospho-c-Jun in HCC, as a read out of JNK activity, was significantly higher (P<0.001) in the non-responder group than in the responder group.
- c-Jun N-terminal kinase activation in HCC was associated with a decreased time to progression and a poor overall survival (P=0.0028 and P=0.0008, respectively).