Abstract C90: Gross appearance of hepatocellular carcinoma reflects expression of cancer stem cells, epithelial-mesenchymal transition, and hypoxia-related genes
Authors: Rhee Hyungjin , Chae Na Deuk , Nyun Park Young 
Published: August 2014

The molecular background for the various gross appearances of hepatocellular carcinoma (HCC) have not yet been clarified, although the prognostic value thereof has been previously reported. Accordingly, in the present study, differences in the expression of cancer stem cells (CSC), epithelial-mesenchymal transition (EMT), and hypoxia related genes, according to the gross type of HCC, were evaluated in two independent cohorts composed of surgically resected HCCs (Cohort 1, n=99; cohort 2, n=110). The gross appearances of HCC were evaluated according to the “General Rules for the Clinical and Pathological Study of Primary Liver Cancer” set by the Liver Cancer Study Group of Japan, and categorized into single nodular (SN) type, single nodular type with extranodular growth (SNEG) type, confluent multinodular (CM) type, and infiltrative (IF) type. Additionally, transcription levels of CSC related genes (EpCAM, Oct3/4, Nanog), EMT regulator (Snail, Twist), and hypoxia related genes (HIF1α, CA9) were evaluated in cohort 1, and the protein expressions of EpCAM and CA9 were evaluated in cohort 2. Clinicopathologic findings, including vascular invasion and capsule formation, as well as prognosis, were also compared according to the gross types of HCC. As observed in this study, IF type HCCs were associated with more frequent portal vein invasion, tumor multiplicity and lack of capsule formation, compared to the other types of HCC (P&lt;0.05 for all), in cohort 1; a similar trend was also identified in cohort 2. In cohort 1, IF type HCCs demonstrated significantly higher transcription levels of EpCAM, Snail and HIF1α (P&lt;0.05 for all) than SN type HCCs. Moreover, the transcription level of HIF1α was also higher in IF type HCCs than both SNEG and CM type HCCs. SN type HCCs exhibited lower transcription levels of EpCAM and Snail compared to CM type and IF type HCCs. In cohort 2, CA9 protein expression was more frequently noted in IF type HCCs than other types of HCC (P&lt;0.05 at all). The expression levels of CSC, EMT and hypoxia related genes showed a tendency to increase in SN, SNEG, CM and IF type HCCs, in that order as like the invasive pathological properties of the HCCs. IF type HCCs showed significantly decreased disease free survival and overall survival in comparison to the other types of HCC in both cohorts 1 and 2. In conclusion, our study demonstrated that IF type HCCs are associated with an increased expression of CSCs, EMT, and hypoxia related genes, all of which are potentially related to their invasive nature and poor prognosis.

Citation Format: Hyungjin Rhee, Na Deuk Chae, Park Young Nyun. Gross appearance of hepatocellular carcinoma reflects expression of cancer stem cells, epithelial-mesenchymal transition, and hypoxia-related genes. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C90.