Transient and etiology-related transcription regulation in cirrhosis prior to hepatocellular carcinoma occurrence.
OBJECTIVE
To search for transcription dysregulation that could (1) differentiate hepatocellular carcinoma (HCC)-free from HCC-related cirrhosis (2) differentiate HCC-free cirrhosis related to HCV from that related to alcohol intake.


METHODS
Using microarray analysis, we compared transcript levels in HCC-free cirrhosis (alcoholism: 7; hepatitis C: 7), HCC-associated cirrhosis (alcoholism: 10; hepatitis C: 10) and eight control livers. The identified transcripts were validated by qRT-PCR in an independent cohort of 45 samples (20 HCC-free cirrhosis; 15 HCC-associated cirrhosis and 10 control livers). We also confirmed our results by immunohistochemistry.


RESULTS
In HCC-free livers, we identified 70 transcripts which differentiated between alcoholic-related cirrhosis, HCV-related cirrhosis and control livers. They mainly corresponded to down-regulation. Dysregulation of Signal Transduction and Activator of Transcription-3 (STAT-3) was found along with related changes in STAT-3 targets which occurred in an etiology-dependent fashion in HCC-free cirrhosis. In contrast, in HCC, such transcription dysregulations were not observed.


CONCLUSIONS
We report that transcriptional dysregulations exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC onset and may be appear like markers from cirrhosis to HCC transition.
Caillot
Frederique
F
Inserm Unite, Faculte de Medecine-Pharmacie, Rouen, France. frederique.caillot@etu.univ-rouen.fr
Derambure
Celine
C
Bioulac-Sage
Paulette
P
Francois
Arnaud
A
Scotte
Michel
M
Goria
Odile
O
Hiron
Martine
M
Daveau
Maryvonne
M
Salier
Jean Philippe
JP
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D010958:Plasminogen