Correlation between tuberous sclerosis complex 2 and glycogen synthase kinase 3 beta levels, and outcomes of patients with hepatocellular carcinoma treated by hepatectomy

Aim: Tuberous sclerosis complex 2 (TSC2), a tumor suppressor, may play an essential role in the regulation of cell growth and cell survival under energy stress conditions. In addition, TSC2 may act in concert with Wnt and energy signals by additional phosphorylation of glycogen synthase kinase 3β (GSK3β) to regulate cell growth. The expression levels and function of TSC2 and GSK3β in hepatocellular carcinoma (HCC) remain unclear.

Methods: The protein levels of TSC2 and GSK3β were measured by immunohistochemistry in normal liver (n = 20), HCC (n = 80) and pericancerous tissues (n = 80). The correlations between TSC2, and GSK3β levels, clinicopathological features and patient survival were also analyzed.

Results: The protein levels of TSC2 and GSK3β in HCC tissues were significantly lower than that in normal liver tissues and pericancerous tissues (P < 0.05). Decreased TSC2 and GSK3β expression was found to be significantly correlated with advanced clinicopathological characteristics and poor prognosis. The results also showed that TSC2 protein levels were associated with GSK3β expression in HCC specimens.

Conclusion: This is the first demonstration that the decreases in TSC2 and GSK3β levels may be associated with vascular invasion, histological grade and tumor-node-metastasis classification.