title: Sequential alterations of microRNA expression in hepatocellular carcinoma development and venous metastasis.
abstract: Hepatocellular carcinoma (HCC) is a prevalent cancer with an extremely high mortality rate attributed to HCC metastasis, which is the major cause of tumor recurrence and organ failure. Presence of tumor thrombi in the portal veins (venous metastases) is a clinicopathological feature of metastatic HCCs. In this study, we analyzed the microRNA (miRNA) expression profiles of nontumorous livers, primary HCCs, and venous metastases in the same livers from 20 HCC patients by way of TaqMan low-density array (TLDA) and identified the precise alterations of miRNA expression from nontumorous livers to primary HCCs and venous metastases globally. By unsupervised clustering analysis, nontumorous livers were distinctly segregated from primary HCCs and venous metastases, whereas no discernible difference in the expression pattern could be found between primary HCCs and venous metastases. However, a marked global reduction of miRNA expression levels was detected in venous metastases, as compared with primary HCCs. These data suggest that miRNA deregulation is an early event in liver carcinogenesis and the later global miRNA down-regulation aggravates the preexisting miRNA deregulation to further promote HCC metastasis.
  
  
  CONCLUSIONS
  Our study has enriched the current understanding of the deregulation of miRNAs in HCC progression and highlighted the sequential and distinctive alterations of miRNA expression in primary HCC and venous metastasis formation.
authors.affiliation: State Key Laboratory for Liver Research and Department of Pathology, Li Ka Shing Faculty Medicine, The University of Hong Kong, Hong Kong. jackwong@pathology.hku.hk
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wong
authors.forename: Carmen Chak-Lui
authors.initials: CC
authors.lastname: Wong
authors.forename: Joyce Man-Fong
authors.initials: JM
authors.lastname: Lee
authors.forename: Dorothy Ngo-Yin
authors.initials: DN
authors.lastname: Fan
authors.forename: Sandy Leung-Kuen
authors.initials: SL
authors.lastname: Au
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
mesh_terms: D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D016000:Cluster Analysis; D015331:Cohort Studies; D016208:Databases, Factual; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D016612:Paraffin Embedding; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D019043:Vascular Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D014680:Veins / Q000473:pathology
chemical_list: D035683:MicroRNAs