title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Qiao
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Le
authors.affiliation: Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Lianghuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000201:enzymology* / Q000235:genetics; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis / Q000235:genetics*; D006498:Hepatectomy; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D038362:Glycogen Synthase Kinase 3