Glycogen Synthase Kinase-3β Is Associated with the Prognosis of Hepatocellular Carcinoma and May Mediate the Influence of Type 2 Diabetes Mellitus on Hepatocellular Carcinoma

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