Abstract
High expression levels of the human sineoculis homeobox homolog 1 (SIX1) gene have been correlated with numerous human malignancies. The SIX1 protein is involved in chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. This study explores the role of SIX1 in tumor progression and in the prognostic evaluation of hepatocellular carcinoma (HCC). Real-time PCR, Western blotting analysis, immunofluorescence (IF) staining, and immunohistochemistry (IHC) were performed to examine SIX1 expression in HCC cell line/tissues compared with adjacent non-tumor and normal liver tissues. Statistical analysis was applied to evaluate the correlation between SIX1 overexpression and the clinicopathological features of HCC. Survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was analyzed using the Cox proportional hazard models. The SIX1 protein was detected in 80.9% of HCCs, which was significantly higher than that in either adjacent non tumor liver or normal liver tissues (P < 0.01). SIX1 overexpression was positively correlated with tumor size, pTNM stage and venous infiltration. Moreover, the 5-year survival rate of patients with high expression of SIX1 was significantly lower than that of patients with low SIX1 expression. Multivariate analysis suggested that pTNM stage and SIX1 protein expression were independent risk factors for survival in HCC. In conclusion, SIX1 plays an important role in the progression of HCC. High level expression of SIX1 is an independent poor prognostic factor of HCC.