Abstract
BackgroundAlthough 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.MethodsFirstly 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.ResultsP-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.ConclusionThe 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.
Highlights
Hepatocellular carcinoma(HCC) is the fifth most common malignancy worldwide and the second most frequent cause of cancer-related mortality [1]
Glycogen synthase kinase 3 (GSK3), a constitutive multifunctional serine threonine kinase, was involved in diversely physiological pathways ranging from insulin signaling pathways which associated with the disease of type 2 diabetes mellitus (T2DM) and Wnt signaling pathways which related to oncogenesis
We found increased protein expression level of total GSK-3b and p-Ser9-GSK-3b in 46 of 60(76.7%)tumor tissues compared with their normal counterparts by western blotting (Fig. 1C)
Summary
Hepatocellular carcinoma(HCC) is the fifth most common malignancy worldwide and the second most frequent cause of cancer-related mortality [1]. Glycogen synthase kinase 3 (GSK3), a constitutive multifunctional serine threonine kinase, was involved in diversely physiological pathways ranging from insulin signaling pathways which associated with the disease of type 2 diabetes mellitus (T2DM) and Wnt signaling pathways which related to oncogenesis [4,5,6,7]. Phosphorylation of Ser9-GSK-3b (p-Ser9-GSK-3b) was associated with the activation of Wnt signaling which could prevent phosphorylation and lead to the stabilization of b-catenin. This mechanism had been reported in a wide range of cancers [9]. Many studies have shown glycogen synthase kinase-3b(GSK-3b) was associated with type 2 diabetes mellitus(T2DM) and implicated with a wide range of cancers, the role of GSK-3b in hepatocellular carcinoma(HCC) and the correlation among GSK-3b, T2DM and HCC remains unclear. Our objectives were to identify the effect of p-Ser9-GSK-3b on the prognosis of patients with HCC and to learn more about the interaction among T2DM, GSK-3b and the prognosis of HCC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
