Abstract 3402: Clinical implication of epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma
Authors: Norio Okumura, Suguru Yamada, Bryan C. Fuchs, Tsutomu Fujii, Hiroyuki Sugimoto, Shuji Nomoto, Shin Takeda, Kenneth K. Tanabe, Yasuhiro Kodera, Akimasa Nakao
Journal: Cancer Research (2012)

Abstract [Background] EMT (epithelial-to-mesenchymal transition) was originally proposed as a process of organogenesis. In recent years, the association between EMT and cancer invasion and metastasis has been advocated and actively investigated in various cancers. In addition, chemoresistance and cancer stemness could be involved in EMT, and the elucidation of this association might contribute to improved outcomes of hepatocellular carcinoma (HCC). We utilized surgical specimens of HCC from our department to examine the clinical implications of EMT. [Methods] One hundred-one patients with hepatocellular carcinoma, who underwent resection in our department between 1994 and 2003 were analyzed. The mRNA expression of E-cadherin and Vimentin were measured by quantitative real-time PCR and EMT status of each patient was determined as follows: Vimentin/E-cadherin &amp;lt; 2 = Epithelial (E), Vimentin/E-cadherin ≤ 2 = Mesenchymal (M). Moreover, transcription factors which are involved in EMT (Twist, Snail, Slug, Zeb-1, and Zeb-2) and also IL-6 and its receptor IL-6R were measured. The correlation between these values and clinicopathological factors and prognosis were analyzed statistically. [Results] 1. AFP values were significantly higher in the epithelial group than in the mesenchymal group (P = 0.029) and PIVKA-II values also tended to be higher in the epithelial group as compared to the mesenchymal group. There was no difference in overall survival, but a significant difference was found in disease-free survival (P = 0.042), which showed that patients with a mesenchymal tumor were more prone to have an earlier recurrence than those with an epithelial tumor. 2. All transcription factors (Twist, Snail, Slug, Zeb-1, and Zeb-2) were more highly expressed in mesenchymal than in epithelial tumors, and in particular, Twist and Zeb-2 were significantly overexpressed (P = 0.0002, P = 0.0017, respectively). Overall survival and disease-free survival of Twist and Zeb-2 expression tumors were examined, but there was no difference between these groups. 3. IL-6 expression was also significantly higher in mesenchymal than in epithelial tumors, but there was no difference in IL-6R expression. [Discussion] Analysis of EMT status in HCC has been performed in the past, but the majority of these studies were done in vitro. Our study using resected surgical specimens suggest that EMT could be involved in cancer invasion and metastasis at the clinical level. In particular, Twist and Zeb-2 might be important for inducing EMT in HCC and patients with mesenchymal tumors are more prone to have early recurrence or metastases after resection. In addition, IL-6 might be an important factor for HCC EMT and could be a potential therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3402. doi:1538-7445.AM2012-3402