Upregulation of DNA repair genes in active cirrhosis associated with hepatocellular carcinoma.
Phenotypic changes in injured livers involve complex network of genes whose interplays may lead to fibrosis and cirrhosis, a major risk of hepatocellular carcinoma. Gene expression profiles in fibrotic livers were analyzed by using cDNA microarray, hierarchical clustering and gene ontology. Analyses of a major cluster of upregulated genes in cirrhosis identified a new set of genes involved in DNA repair and damage. The upregulation of DNA repair genes was confirmed by real-time quantitative polymerase chain reaction and associated with necroinflammatory activity (P<0.001). Increased DNA repair activity in cirrhosis with inflammatory activity may reflect increased DNA damages as a consequence of chronic liver injury.
Zindy
Pierre
P
INSERM U620, Détoxication et Réparation Tissulaire, Facultés de Médecine et Pharmacie, Université de Rennes I, 2 Av. Léon Bernard, 35043 Rennes Cedex, France.
Andrieux
Lise
L
Bonnier
Dominique
D
Musso
Orlando
O
Langouët
Sophie
S
Campion
Jean Pierre
JP
Turlin
Bruno
B
Clément
Bruno
B
Théret
Nathalie
N
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C071447:ERCC1 protein, human; D004720:Endonucleases