Genome-wide differences in hepatitis C- vs alcoholism-associated hepatocellular carcinoma.
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.
Derambure
Celine
C
Inserm Unite 519, Faculte de Medecine-Pharmacie, 22 Bvd Gambetta, Rouen cedex 76183, France. celine.derambure1@univ-rouen.fr
Coulouarn
Cedric
C
Caillot
Frederique
F
Daveau
Romain
R
Hiron
Martine
M
Scotte
Michel
M
Francois
Arnaud
A
Duclos
Celia
C
Goria
Odile
O
Gueudin
Marie
M
Cavard
Catherine
C
Terris
Benoit
B
Daveau
Maryvonne
M
Salier
Jean-Philippe
JP
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
D012333:RNA, Messenger