Objective  This study aims to investigate the expression of dual specificity phosphatase 6 (DUSP6) in hepatocellular carcinoma (HCC) and the correlation of DUSP6 with the mitogen-activated protein kinase signaling pathway and clinicopathological characteristics.

  Methods  The expressions of DUSP6, p-ERK, p-JNK, p-P38α, CyclinD1, and Ki-67 were assessed via immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissue from 305 patients who had undergone hepatectomy for HCC. Statistical analysis was performed to assess the relationship between DUSP6 and others or the clinicopathologic factors.

  Results  The DUSP6 expression was significantly higher in the tumor tissue compared with that in the peritumor or normal liver tissue (P < 0.001). The expression of p-ERK, p-JNK, and Ki-67 was significantly different between the tumor and the peritumor (P < 0.001). Spearman correlation analysis demonstrated that the DUSP6 expression positively correlated with p-ERK, CyclinD1, and Ki-67 (r=0.179, P < 0.01; r=0.213, P < 0.01; r=0.137, P < 0.05). DUSP6 expression was significantly associated with hepatitis B and liver cirrhosis history for the group with relative tumor expression (P=0.034 and P=0.044, respectively).

  Conclusion  DUSP6 expression in HCC was overexpressed compared with that in peritumor or normal liver tissue. DUSP6 may provide a negative feedback regulation to the p-ERK overexpression in HCC. The DUSP6 overexpression may have a role in regulating the cell cycle and promoting the proliferative activity of HCC.