Decreased expression of SOX6 confers a poor prognosis in hepatocellular carcinoma

SOX6, a member of the D subfamily of sex determining region y-related transcription factors, plays critical roles in cell fate determination, differentiation and proliferation. It has been identified as a tumor suppressor or an oncogene in different human cancers. However, the role of SOX6 in the development and progression of hepatocellular carcinoma (HCC) has not been explored. The aim of this study was to investigate the expression of SOX6 in HCC and determine its correlation with tumor progression and prognosis.

130 HCC patients who had undergone curative liver resection were selected and immunohistochemistry, Western blotting, and quantitative real time polymerase chain reaction (Q-PCR) were performed to analyze SOX6 expression in the respective tumors.

Q-PCR, immunohistochemistry and Western blotting consistently confirmed the decreased expression of SOX6 at both mRNA and protein levels in HCC tissues compared with their adjacent nonneoplastic tissues (P<0.01). Additionally, the expression of SOX6, determined by immunohistochemistry, was negatively correlated with the tumor stage (P=0.003) and serum AFP (P=0.02). Moreover, HCC patients with lower SOX6 expression had worse 5-year disease-free survival and 5-year overall survival than those with high SOX6 expression (P=0.006 and 0.001, respectively). Furthermore, the Cox proportional hazards model showed that the decreased expression of SOX6 was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR]=2.398, 95% confidence interval [CI]=1.601-5.993, P=0.01) and 5-year overall survival (HR=3.569, CI=1.381-7.290, P=0.008) in HCC.

These findings provide evidence for the first time that SOX6 expression was decreased in HCC, which correlated with poor prognosis, suggesting that SOX6 may be a novel and potential prognostic marker for HCC.