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Genome-wide differences in hepatitis C- vs alcoholism-associated hepatocellular carcinoma

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Author(s): Céline Derambure, Cédric Coulouarn, Frédérique Caillot, Romain Daveau, Martine Hiron, Michel Scotte, Arnaud François, Celia Duclos, Odile Goria, Marie Gueudin, Catherine Cavard, Benoit Terris, Maryvonne Daveau, Jean-Philippe Salier

Journal: World Journal of Gastroenterology
ISSN 1007-9327

Volume: 14;
Issue: 11;
Start page: 1749;
Date: 2008;
Original page

Keywords: Alcoholism | Chromosome | Cirrhosis | Hepatitis C | Transcriptomes | Protein function

ABSTRACT
AIM: 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.CONCLUSION: Etiology-specific abnormalities (chromosome 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.
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