Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16.

Abstract

Inhibitor of differentiation/DNA binding protein 1 (Id-1) plays a pivotal role in the regulation of cell proliferation and carcinogenesis via inhibiting basic helix-loop-helix (HLH) transcription factors. Recently, Id-1 was found to repress p16 in tumorous tissue specimens including hepatocellular carcinoma (HCC), but its relevance in precancerous liver tissues is unknown. Id-1 expression in the liver tissue specimens of 112 patients with cirrhosis without HCC was studied by immunohistochemical analysis. Correlations were investigated between Id-1 expression and clinicopathologic features, the status of p16, and the risk of HCC occurrence. A high expression of Id-1 was observed in 42 patients (38%). The level of Id-1 expression was not associated with clinical standard parameters or the status of p16 in cirrhotic tissue specimens. The cumulative incidence of HCC development was significantly higher in a group of patients with high Id-1 expression (P = 0.0008). Multivariate analysis revealed that increased Id-1 expression is an independent significant factor for the risk of HCC development in patients with cirrhosis (relative risk = 2.75, P = 0.003). The results of the current study suggested that increased expression of Id-1 may play an important role in the early step of hepatocarcinogenesis, and might serve as a useful marker for determining patients with cirrhosis with a high risk of HCC occurrence.