Glycogen synthase kinase-3? is associated with the prognosis of hepatocellular carcinoma and may mediate the influence of type 2 diabetes mellitus on hepatocellular carcinoma.

ABSTRACT: BACKGROUND: Although many studies have shown glycogen synthase kinase-3? (GSK-3?) was associated with type 2 diabetes mellitus (T2DM) and implicated with a wide range of cancers, the role of GSK-3? in hepatocellular carcinoma(HCC) and the correlation among GSK-3?, T2DM and HCC remains unclear. Our objectives were to identify the effect of p-Ser9-GSK-3? on the prognosis of patients with HCC and to learn more about the interaction among T2DM, GSK-3? and the prognosis of HCC. METHODS: Firstly we used reverse transcriptase-PCR(RT-PCR) and western blotting to determine the expression levels of GSK-3? and p-Ser9-GSK-3? in human HCC samples. We then used immunohistochemical staining to evaluate the expression pattern of p-Ser9-GSK-3? in 178 patients with HCC after curative partial hepatectomy. Finally we statistically analyzed the association of p-Ser9-GSK-3? and T2DM with the prognosis of patients with HCC. RESULTS: P-Ser9-GSK-3? was over-expressed in tumor tissues compared with their normal counterparts. Correlation and regression analysis indicated that the over-expression of p-Ser9-GSK-3? was significantly associated with T2DM, and the correlation coefficient was 0.259 (P?=?0.001). Multivariate analysis showed that the over-expression of p-Ser9-GSK-3?(P<0.001) and T2DM(P?=?0.008) were independently associated with poor prognosis of HCC, respectively. Further analysis demonstrated that these two variables are closely related with each other. CONCLUSION: The over-expression of p-Ser9-GSK-3? and T2DM are strongly correlated with worse surgical outcome of HCC. P-Ser9-GSK-3? may play a significant role in mediating the influence of T2DM on the prognosis of HCC.

SUBMITTER: Qiao G 

PROVIDER: S-EPMC4144855 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature