title: Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma.
abstract: Although HCC is the third-leading cause of cancer-related deaths worldwide, there is only an elemental understanding of its molecular pathogenesis. In western countries, HCV infection is the main etiology underlying this cancer's accelerating incidence. To characterize the molecular events of the hepatocarcinogenic process, and to identify new biomarkers for early HCC, the gene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from preneoplastic lesions (cirrhosis and dysplasia) to HCC, including 4 neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. We identified gene signatures that accurately reflect the pathological progression of disease at each stage. Eight genes distinguish between control and cirrhosis, 24 between cirrhosis and dysplasia, 93 between dysplasia and early HCC, and 9 between early and advanced HCC. Using quantitative real-time reverse-transcription PCR, we validated several novel molecular tissue markers for early HCC diagnosis, specifically induction of abnormal spindle-like, microcephaly-associated protein, hyaluronan-mediated motility receptor, primase 1, erythropoietin, and neuregulin 1. In addition, pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then upregulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages.
  
  
  CONCLUSIONS
  These findings provide a comprehensive molecular portrait of genomic changes in progressive HCV-related HCC.
authors: Mount Sinai Liver Cancer Program, Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. elisa.wurmbach@mssm.edu
authors: Elisa
authors: E
authors: Wurmbach
authors: Ying-bei
authors: YB
authors: Chen
authors: Greg
authors: G
authors: Khitrov
authors: Weijia
authors: W
authors: Zhang
authors: Sasan
authors: S
authors: Roayaie
authors: Myron
authors: M
authors: Schwartz
authors: Isabel
authors: I
authors: Fiel
authors: Swan
authors: S
authors: Thung
authors: Vincenzo
authors: V
authors: Mazzaferro
authors: Jordi
authors: J
authors: Bruix
authors: Erwin
authors: E
authors: Bottinger
authors: Scott
authors: S
authors: Friedman
authors: Samuel
authors: S
authors: Waxman
authors: Josep M
authors: JM
authors: Llovet
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018816:Genes, cdc; D015894:Genome, Human; D006526:Hepatitis C / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor