title: RNA-Seq analyses generate comprehensive transcriptomic landscape and reveal complex transcript patterns in hepatocellular carcinoma.
abstract: RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome at both gene and exon levels and with a unique ability of identifying novel splicing variants. To date, RNA-seq analysis of HBV-related hepatocellular carcinoma (HCC) has not been reported. In this study, we performed transcriptome analyses for 10 matched pairs of cancer and non-cancerous tissues from HCC patients on Solexa/Illumina GAII platform. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for samples sequenced on each lane, which was able to identify >50% of all the annotated genes for each sample. Furthermore, we identified 1,378 significantly differently expressed genes (DEGs) and 24, 338 differentially expressed exons (DEEs). Comprehensive function analyses indicated that cell growth-related, metabolism-related and immune-related pathways were most significantly enriched by DEGs, pointing to a complex mechanism for HCC carcinogenesis. Positional gene enrichment analysis showed that DEGs were most significantly enriched at chromosome 8q21.3-24.3. The most interesting findings were from the analysis at exon levels where we characterized three major patterns of expression changes between gene and exon levels, implying a much complex landscape of transcript-specific differential expressions in HCC. Finally, we identified a novel highly up-regulated exon-exon junction in ATAD2 gene in HCC tissues. Overall, to our best knowledge, our study represents the most comprehensive characterization of HBV-related HCC transcriptome including exon level expression changes and novel splicing variants, which illustrated the power of RNA-seq and provided important clues for understanding the molecular mechanisms of HCC pathogenesis at system-wide levels.
authors: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors: Qichao
authors: Q
authors: Huang
authors: Biaoyang
authors: B
authors: Lin
authors: Hanqiang
authors: H
authors: Liu
authors: Xi
authors: X
authors: Ma
authors: Fan
authors: F
authors: Mo
authors: Wei
authors: W
authors: Yu
authors: Lisha
authors: L
authors: Li
authors: Hongwei
authors: H
authors: Li
authors: Tian
authors: T
authors: Tian
authors: Dong
authors: D
authors: Wu
authors: Feng
authors: F
authors: Shen
authors: Jinliang
authors: J
authors: Xing
authors: Zhi-Nan
authors: ZN
authors: Chen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger