Abstract 171: Deciphering the role of long noncoding RNAs in the progression of hepatocellular carcinoma using next-generation sequencing
Authors: Degli Esposti Davide , Voegele Catherine , Cahais Vincent , Forey Nathalie , Le Calvez Kelm Florence , McKay James , Hernandez-Vargas Hector , Herceg Zdenko 
Published: August 2015

Hepatocellular carcinoma (HCC) is the second most common cause of death from cancer worldwide, estimated to be responsible for nearly 746,000 deaths in 2012 representing 9.1% of the total cancer-related deaths. Incidence rates of HCC continue to increase in North America and Europe with a slight decrease in Asia. It is currently accepted that epigenetic alterations are critical in cancer development in humans, including HCC. Among the different layers of epigenetic control, long non coding RNAs (lncRNAs) have been steadily gaining prominence in recent years. LncRNAs have emerged as critical regulators of the gene expression and growing evidence points to their tissues and tumour specificity and that their deregulation may represent early event in tumour development. Several recent reports have implicated lncRNAs in HCC development, such as HULC or H19, although the biological and molecular mechanisms by which lncRNAs contributes to liver cancer development remain poorly understood.. The purpose of this study is to perform a global profiling of lncRNAs in HCC using Next Generation Sequencing in order to improve the understanding of lncRNAs’ role in HCC and to provide new biologically sound candidate biomarkers for the identification of patients at higher risk of developping HCC. We have performed RNA-Sequencing (RNA-Seq) of tumor tissues and paired-matched surrounding non-tumor (cirrhotic) tissues from 10 patients and normal livers from 3 patients operated for liver metastases. Based on our first results, we observed a global decrease in the number of lncRNAs expressed in cirrhotic and tumor tissues compared with normal livers. We identified 41 lncRNAs differentially expressed in HCC compared to matched non-tumour tissues, most of whom have not been reported previously. We identified also more than 700 coding genes differentially expressed in HCC compared to their non-tumor counterparts. We compared our results on the coding trascriptome with RNA-Seq data from 44 cases of HCC (paired-matched tumor and non tumor tissues) available in The Cancer Genome Atlas (TCGA) dataset and found that more than 70% of the genes identified in our study overlap with differentially expressed genes identified in the TCGA dataset.

Our results suggest that lncRNAs may be involved in the homeostasis of the hepatic tissue and that the loss of their expression is associated with tissue regeneration and transformation.

Citation Format: Davide Degli Esposti, Catherine Voegele, Vincent Cahais, Nathalie Forey, Florence Le Calvez Kelm, James McKay, Hector Hernandez-Vargas, Zdenko Herceg. Deciphering the role of long noncoding RNAs in the progression of hepatocellular carcinoma using next-generation sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 171. doi:10.1158/1538-7445.AM2015-171