Abstract 3371: Expression levels of EMT-related genes in hepatocellular carcinoma

Abstract

Abstract Epithelial-Mesenchymal Transition (EMT) has been recognized as a cellular process by which epithelial cells undergo mesenchymal phenotype leading to increased motility and invasion in cancer cells. We recently have reported that sorafenib exerts a potent inhibitory activity against the EMT by inhibiting MAPK signaling and SNAI1 expression in hepatocellular carcinoma (HCC). Large-scale clinical data on SNAI1 expression and the prognosis of patients with HCC was recently reported, and the overexpression of Snail and/or Twist was correlated with a worse prognosis. However, it remains largely unclear on clinico-pathological features of other EMT-related genes and whether these genes are overexpressed in HCC compared with paired non-cancer lesion of the liver. Here, we examined the mRNA expression levels of EMT-related genes including SNAI1/Snail, SNAI2/slug, ZEB1/TCF8, ZEB2/SIP1, TWIST, CDH1/E-cadherin, CDH2/N-cadherin, VIM/vimentin and FN1/fibronectin in HCC. RNA was extracted from frozen surgical HCC samples (n=48) and their paired liver samples (n=14). Real-time RT-PCR amplification was performed. Glyceraldehyde 3-phosphate dehydrogenase (GAPD) was used to normalize the expression levels in the subsequent quantitative analyses. E-cadherin was significantly downregulated in most of HCC (12/14) and those of 5 HCC were markedly downregulated below 25% of paired liver. Interestingly, we found that ZEB1 is tended to be upregulated in HCC, while ZEB2 was downregulated. Regarding EMT-inducible transcription factors, SNAI1, SNAI2, ZEB1, ZEB2 and TWIST, these expression levels were overexpressed in several HCC samples. In conclusion, our findings indicate that some HCC subpopulation actually undergo EMT via upregulation of SNAI1, SNAI2, ZEB1, ZEB2 and TWIST. Evaluation of clinico-pathological features on these expression and analysis of additional HCC samples up to 100 cases are now under way. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3371. doi:10.1158/1538-7445.AM2011-3371