It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c-Met/hepatocyte growth factor signaling. However, the role of CD151 alone and coexpression of CD151/c-Met in hepatocellular carcinoma (HCC) remains unclear. We found that expression of CD151 was positively related to metastatic potential of HCC cell lines, and modified cells with CD151 high showed higher secretion of matrix metalloproteinase 9 and aggressiveness in vitro and higher metastatic ability in vivo. Furthermore, HCC patients with vascular invasion, large tumors, multiple tumors, high tumor-node-metastasis stage, and undifferentiated tumor were prone to have higher CD151 expression. The postoperative 3-, 5-, and 7-year overall survival (OS) of patients in HCCs with CD151 high were significantly lower than those in the CD151 low group, and correspondingly cumulative recurrence rates in HCCs with CD151 high were significantly higher than those in the CD151 low group. Both CD151 and c-Met were remarkably overexpressed in HCCs, compared with adjacent nontumorous and normal liver tissues. Pearson correlation analysis showed a slight correlation between CD151 and c-Met in HCCs. Importantly, the 5-and 7-year OS rates in CD151 high /c-Met high patients were 50.5% and 37.8%, respectively, significantly lower than those of CD151 low /c-Met low patients (63.9% and 54.6%, respectively). Five-and 7-year cumulative recurrence rates in CD151 high /c-Met high patients were 53.3% and 71.9%, respectively, markedly higher than those of CD151 low / c-Met low patients (39.0% and 52.5%, respectively). Multivariate analysis revealed that CD151 and combination of CD151/c-Met were independent prognostic indicators for OS and cumulative recurrence. Conclusion: CD151 is positively associated with invasiveness of HCC, and CD151 or combination of CD151/c-Met is a novel marker in predicting the prognosis of HCC and a potential therapeutic target. (HEPATOLOGY 2009;49:491-503.)

Our study results demonstrated for the first time the existence of genetic polymorphisms of OCT2 in the Chinese population, and further showed that the 808G>T polymorphism is associated with a reduced metformin renal or tubular clearance. Moreover, the inhibition of metformin renal tubular secretion by cimetidine also appeared to be dependent on this mutation.

These data suggest that the SATB1 gene may play an important role in the development and progression of liver cancer by regulation of genes related to cell cycle progression, apoptosis and EMT.