title: Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCC-related genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition, no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.
authors.affiliation: Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009687:Nuclear Proteins / Q000235:genetics; D009857:Oncogenes; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011379:Prognosis; D011971:Receptors, Immunologic / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics; D000077157:Sorafenib; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D016896:Treatment Outcome; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D018797:Cell Cycle Proteins; D015850:Interleukin-6; C544162:MACC1 protein, human; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D010671:Phenylurea Compounds; D011971:Receptors, Immunologic; C122167:TPX2 protein, human; C408842:TREM1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D009536:Niacinamide; D000077157:Sorafenib; D056564:Sirtuin 1
keywords: DNA methylation; Hepatocellular carcinoma; MicroRNA; Oncogene; Tumor suppressor gene