Higher intratumor than peritumor expression of DUSP6/MKP-3 is associated with recurrence after curative resection of hepatocellular carcinoma.

Background The MAPK phosphatases (MKPs) are a family of dual-specificity phosphatases (DUSPs) that can dephosphorylate both phosphothreonine and phosphotyrosine residues, thus inactivating MAPK signaling. DUSP6 is a cytoplasmic MKP that can inactivate ERK. DUSP6 has been implicated in the development of some tumors. The aim of this research was to investigate the expression of DUSP6 in hepatocellular carcinoma (HCC) and the correlation of DUSP6 with mitogen-activated protein kinases (MAPKs), clinicopathological characteristics, and prognosis. Methods Tissues from 305 patients who had undergone hepatectomy for HCC was used in this study. The expression of DUSP6, p-ERK, p-JNK, and p-p38 alpha was determined using tissue microarrays for immunohistochemical analysis. The prognostic value of DUSP6 and other clinicopathological factors were evaluated. Results The expression of DUSP6 was significantly higher in the tumor tissue when compared to the peritumor or normal liver tissue (P<0.001). Tumor DUSP6 expression was significantly associated with disease-free survival (DFS) (P=0.013). Tumor DUSP6 expression was an independent prognostic factor for DFS (Hazard ratio = 1.635, P=0.006). Conclusions DUSP6 is over expressed in tumor tissue compared to peritunnor or normal liver tissue. Higher expression of DUSP6 in tumor tissue, than in peritumor tissue, is associated with the recurrence after curative resection of HCC, and the relative tumor DUSP6 expression has good power to predict the recurrence of HCC.