Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma

Background/Aims: Metabolic dysregulation is one of the risk factors for the development of hepatocellular carcinoma (HCC). We investigated the activated metabolic pathway in HCC to identify its role in HCC growth and mortality. Methods:Gene expression profiles of HCC tissues and non-cancerous liver tissues were obtained by serial analysis of gene expression. Pathway analysis was performed to characterize the metabolic pathway activated in HCC. Suppression of the activated pathway by RNA interference was used to evaluate its role in HCC in vitro. Relation of the pathway activation and prognosis was statistically examined. Results: A total of 289 transcripts were up- or down-regulated in HCC compared with non-cancerous liver (P < 0.005). Pathway analysis revealed that the lipogenic pathway regulated by sterol regulatory element binding factor 1 (SREBF1) was activated in HCC, which was validated by real-time RT-PCR. Suppression of SREBF1 induced growth arrest and apoptosis whereas overexpression of SREBF1 enhanced cell proliferation in human HCC cell lines. SREBF1 protein expression was evaluated in 54 HCC samples by immunohistochemistry, and Kaplan-Meier survival analysis indicated that SREBF1-high HCC correlated with high mortality. Conclusions:The lipogenic pathway is activated in a subset of HCC and contributes to cell proliferation and prognosis. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.