title: Identification of latent biomarkers in hepatocellular carcinoma by ultra-deep whole-transcriptome sequencing.
abstract: There is an urgent need to identify biomarkers for hepatocellular carcinoma due to limited treatment options and the poor prognosis of this common lethal disease. Whole-transcriptome shotgun sequencing (RNA-Seq) provides new possibilities for biomarker identification. We sequenced ∼250 million pair-end reads from a pair of adjacent normal and tumor liver samples. With the aid of bioinformatics tools, we determined the transcriptome landscape and sought novel biomarkers by further empirical validations in 55 pairs of adjacent normal and tumor liver samples with various viral statuses such as HBV(+), HCV(+) and HBV(-)HCV(-). We identified a novel gene with coding regions, termed DUNQU1, which has a tissue-specific expression pattern in tumor liver samples of HCV(+) and HBV(-)HCV(-) hepatocellular carcinomas. Overexpression of DUNQU1 in Huh7 cell lines enhances the ability to form colonies in soft agar. Also, we identified three novel differentially-expressed protein-coding genes (ALG1L, SERPINA11 and TMEM82) that lack documented expression profiles in liver cancer and showed that the level of SREPINA11 is correlated with pathology stages. Moreover, we showed that the alternative splicing event of FGFR2 is associated with virus infection, tumor size, cirrhosis and tumor recurrence. The findings indicate that these new markers of hepatocellular carcinoma may be of value in improving prognosis and could have potential as new targets for developing new treatment options.
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: K-T
authors.initials: KT
authors.lastname: Lin
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Shann
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: G-Y
authors.initials: GY
authors.lastname: Chau
authors.affiliation: 1] Institute of Information Science, Academia Sinica, Taipei, Taiwan [2] USC/Information Sciences Institute, Marina del Rey, CA, USA [3] Division of Biomedical Informatics, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: C-N
authors.initials: CN
authors.lastname: Hsu
authors.affiliation: 1] Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan [2] Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan [3] Cancer Research Center and Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: C-Y F
authors.initials: CY
authors.lastname: Huang
mesh_terms: D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2