Correlation of PTEN/AKT status in bone microenviroment and bone metastasis of hepatocellular carcinoma

Abstract

Objective To investigate the effect and mechanism of PTEN and its associated AKT signal pathway in bone metastasis of hepatocellular carcinoma (HCC). Methods 89 cases of HCC tumor specimens, including 22 cases with hilar lymph node metastasis, 35 cases with bone metastasis and 32 cases without metastasis, were collected. and the expression levels of PTEN, total AKT (t-AKT) and phosphorylated AKT (p-AKT) were tested by western blotting and immunohistochemical staining. The relationship between PTEN/AKT and clinicopathological parameters of HCC patients was analyzed. Kaplan-Meier and log-rank were used to analyze their progression-free survival (PFS) and overall survival (OS). Results The expression levels of PTEN was correlated with bone metastasis of HCC, but was not with lymph node metastasis. The phosphorylated AKT (p-AKT) was correlated with bone metastasis and lymph metastasis of HCC. The expression levels of PTEN and p-AKT in HCC were in reverse parallel. PTEN expression was weak or negative in HCC cells of bone metastasis foci, however p-AKT expression was significantly positive, and PTEN expression of interstitial cells in the microenvironment of bone metastasis foci was significantly decreased. Kaplan-Meier survival curve and log-rank analysis showed that PTEN expression level was significantly correlated with PFS and OS (PFS: P=0.030; OS: P=0.026). The level of p-AKT was also significantly correlated with PFS and OS (PFS: P=0.007; OS: P=0.022). Conclusions PTEN inactivation and AKT phosphorylation activation play an important role in HCC metastasis, especially in bone metastasis. The decreased expression level of PTEN in bone microenvironment as a factor inducing condition of bone metastasis of HCC. Key words: Hepatocellular carcinoma; Bone metastasis; PTEN; AKT pathway