A Study On The Relativity Of Clinicopathological Features, MAPK Signaling Pathway And Prognosis About DUSP6 Expression In Hepatocellular Carcinoma

Objective:To investigate the correlation of expression of DUSP6 with clinicopathological features, MAPK signaling pathway and prognosis in hepatocellular carcinoma (HCC).Methods:1)The Expressions of DUSP6, p-ERK, p-JNK, p-P38a, CyclinDl and Ki-67 were assessed by 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.2) Prognostic value of DUSP6 and other clinicopathologic factors were evaluated.Results:1) The expression of DUSP6 was significant different among tumor, peritumor and normal liver tissue (P<0.001).The expression of p-ERK,p-JNK and Ki-67 was significant different between tumor and peritumor respectively (P<0.001); the expression of p-P38αand CyclinDl was no significant difference between tumor and peritumor respectively (P=0.271,P=0.828).The results of Spearman correlation analysis demonstrated that DUSP6 and p-ERK remained significant positive correlation (r=0.179,P<0.01);there was no significant correlation between DUSP6 and p-JNK(r=0.074,P>0.05),between DUSP6 and p-P38a (r=0.095,P>0.05); DUSP6 and CyclinDl remained significant positive correlation (r=0.213,P<0.01); DUSP6 and Ki-67 remained significant positive correlation (r=0.137,P<0.05).2) DUSP6 expression was not associated with clinicopathological features in group of tumor expression and relative tumor expression (P>0.05),except hepatitis B and liver cirrhosis history in group of relative tumor expression (P<0.05).Kaplan-Meier analyzed, tumor DUSP6 expression was not associated with overall survival (OS) or disease-free survival (DFS);relative tumor DUSP6 expression was not associated with OS but was significantly associated with DFS (P=0.004).With univariate Analyses, tumor size, intrahepatic metastasis, microvascular invasion,tumor differentiation, TNM stage were associated with OS and DFS;but AFP was only associated with OS, and tumor DUSP6 expression and relative tumor DUSP6 expression were only associated with DFS.With multivariate analyses of Cox proportional hazards regression model, tumor size and tumor differentiation were independent prognostic factors for OS (P<0.001 and P=0.006, respectively); tumor size, intrahepatic metastasis and relative tumor DUSP6 expression were independent prognostic factors for DFS (P<0.001,P=0.039 and P=0.006, respectively).Conclusions:1)The expression of DUSP6 in tumor is up-regulated compared with peritumor and normal liver tissue, which indicates that DUSP6 may be gradually up-regulated during genesis and development of HCC.The expression of p-ERK and p-JNK in tumor is significantly up-regulated compared with peritumor, but there is no significant difference between tumor and peritumor for p-P38a, that explains up-regulated expression of p-ERK and p-JNK is concerned with genesis and development of HCC but P38a is not; there is no significant difference between tumor and peritumor about the expression of CyclinDl,which indicates that CyclinDl may have nothing to do with genesis and development of HCC;the expression of Ki-67 in tumor is significantly increased compared with peritumor, which indicates that the proliferation of HCC is higher than peritumor cirrhosis and normal liver tissue. DUSP6 and p-ERK remain significant positive correlation but there is no significant correlation between DUSP6 and p-JNK or p-P38a, so DUSP6 maybe assume negative feedback regulation to overexpression of p-ERK.The positive correlation between DUSP6 and CyclinDl hints the closer relationship between them and further study is needed.The positive correlation between DUSP6 and Ki-67 maybe result from the activation of ERK signaling pathway.2) HBV infection or cirrhosis may be associated with DUSP6;high relative tumor DUSP6 expression is associated with recurrence after curative resection of HCC;relative tumor DUSP6 expression can have a best power to predict the recurrence of HCC;DUSP6 may be a target of postoperative adjuvant therapy.