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Identification of differentially expressed genomic repeats in primary hepatocellular carcinoma and their potential links to biological processes and survival

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. Research on HCC so far primarily focused on genes and provided limited information on genomic repeats, which constitute more than half of the human genome and contribute to genomic stability. In line with this, repeat dysregulation was significantly shown to be pathological in various cancers and other diseases. In this study, we aimed to determine the full repeat expression profile of HCC for the first time. We utilised two independent RNA-seq datasets obtained from primary HCC tumours with matched normal tissues of 20 and 17 HCC patients, respectively. We quantified repeat expressions and analysed their differential expression. We also identified repeats that are cooperatively expressed with genes by constructing a gene coexpression network. | Turkish Journal of Biology Turk J Biol 2021 45 599-612 http journals.tubitak.gov.tr biology TÜBİTAK Research Article doi 10.3906 biy-2104-13 Identification of differentially expressed genomic repeats in primary hepatocellular carcinoma and their potential links to biological processes and survival 1 2 1 3 Gökhan KARAKÜLAH Cihangir YANDIM 1 İzmir Biomedicine and Genome Center İBG İzmir Turkey 2 İzmir International Biomedicine and Genome Institute İBG-İzmir Dokuz Eylül University İzmir Turkey 3 Department of Genetics and Bioengineering Faculty of Engineering İzmir University of Economics İzmir Turkey Received 05.04.2021 Accepted Published Online 19.06.2021 Final Version 18.10.2021 Abstract Hepatocellular carcinoma HCC is one of the deadliest cancers. Research on HCC so far primarily focused on genes and provided limited information on genomic repeats which constitute more than half of the human genome and contribute to genomic stability. In line with this repeat dysregulation was significantly shown to be pathological in various cancers and other diseases. In this study we aimed to determine the full repeat expression profile of HCC for the first time. We utilised two independent RNA-seq datasets obtained from primary HCC tumours with matched normal tissues of 20 and 17 HCC patients respectively. We quantified repeat expressions and analysed their differential expression. We also identified repeats that are cooperatively expressed with genes by constructing a gene coexpression network. Our results indicated that HCC tumours in both datasets harbour 24 differentially expressed repeats and even more elements were coexpressed with genes involved in various metabolic pathways. We discovered that two L1 elements L1M3b L1M3de were downregulated and a handful of HERV subfamily repeats HERV-Fc1-int HERV3-int HERVE_a-int HERVK11D-int HERVK14C-int HERVL18-int were upregulated with the exception of HERV1_LTRc which was downregulated. Various LTR elements LTR32 LTR9 LTR4 .