title: Genome-wide differences in hepatitis C- vs alcoholism-associated hepatocellular carcinoma.
abstract: OBJECTIVE
  To look at a comprehensive picture of etiology-dependent gene abnormalities in hepatocellular carcinoma in Western Europe.
  
  
  METHODS
  With a liver-oriented microarray, transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism, 12; hepatitis C, 10) and 5 controls. Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set (12 + 10) and a test set (6 + 7).
  
  
  RESULTS
  A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism) or -2 (hepatitis C) and ontology indicated a predominant inflammatory response (alcoholism) or changes in cell cycle regulation, transcription factors and interferon responsiveness (hepatitis C). A stringent selection of 23 transcripts whose differences between etiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis. These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors.
  
  
  CONCLUSIONS
  Etiology-specific abnormalities (chromo-some preference; differences in transcriptomes and related functions) have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C. This may open novel avenues for differential therapies in this disease.
authors: Inserm Unite 519, Faculte de Medecine-Pharmacie, 22 Bvd Gambetta, Rouen cedex 76183, France. celine.derambure1@univ-rouen.fr
authors: Celine
authors: C
authors: Derambure
authors: Cedric
authors: C
authors: Coulouarn
authors: Frederique
authors: F
authors: Caillot
authors: Romain
authors: R
authors: Daveau
authors: Martine
authors: M
authors: Hiron
authors: Michel
authors: M
authors: Scotte
authors: Arnaud
authors: A
authors: Francois
authors: Celia
authors: C
authors: Duclos
authors: Odile
authors: O
authors: Goria
authors: Marie
authors: M
authors: Gueudin
authors: Catherine
authors: C
authors: Cavard
authors: Benoit
authors: B
authors: Terris
authors: Maryvonne
authors: M
authors: Daveau
authors: Jean-Philippe
authors: JP
authors: Salier
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D002889:Chromosomes, Human, Pair 2; D002898:Chromosomes, Human, Pair 8; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000235:genetics / Q000821:virology; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications* / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results
chemical_list: D012333:RNA, Messenger