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-p38α 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 peritumor 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.
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Bo
B
Yang
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Yunshan
Y
Tan
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, the Chinese Ministry of Education, Shanghai 200032, China.
Huichuan
H
Sun
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, the Chinese Ministry of Education, Shanghai 200032, China.
Jia
J
Fan
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, the Chinese Ministry of Education, Shanghai 200032, China.
Zhaoyou
Z
Tang
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Email: newera_ji@yahoo.com.
Yuan
Y
Ji
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D054642:Dual Specificity Phosphatase 6 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D046888:Tissue Array Analysis; D055815:Young Adult
C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6