Caillot F, Derambure C, Bioulac-Sage P, François A, Scotte M, Goria O, Hiron M, Daveau M, Salier JP. Transient and etiology-related transcription regulation in cirrhosis prior to hepatocellular carcinoma occurrence. World J Gastroenterol 2009; 15(3): 300-309 [PMID: 19140229 DOI: 10.3748/wjg.15.300]
Corresponding Author of This Article
Frédérique Caillot, Inserm Unité 905, Faculté de Médecine-Pharmacie, 22 Bvd Gambetta, 76183 Rouen cedex, France. frederique.caillot@etu.univ-rouen.fr
Article-Type of This Article
Original Articles
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Frédérique Caillot, Céline Derambure, Martine Hiron, Maryvonne Daveau, Jean-Philippe Salier, Inserm Unité 905 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Faculté de Médecine-Pharmacie, 76183 Rouen, France
Paulette Bioulac-Sage, Service d’Anatomie Pathologique, Centre Hospitalier Universitaire, and Inserm U889, 33000 Bordeaux, France
Arnaud François, Département Pathologie, Centre Hospitalier Universitaire, 76183 Rouen, France
Michel Scotte, Service de Chirurgie Générale et Digestive, Centre Hospitalier Universitaire, 76183 Rouen, France
Odile Goria, Service d’Hépato-gastro-entérologie, Centre Hospitalier Universitaire, 76183 Rouen, France
Author contributions: Caillot F, Daveau M and Salier JP designed the study; Caillot F and Hiron M performed the research; Bioulac-Sage P, François A, Scotte M and Goria O contributed to sample collection; Caillot F, Derambure C, Daveau M and Salier JP wrote the paper.
Correspondence to: Frédérique Caillot, Inserm Unité 905, Faculté de Médecine-Pharmacie, 22 Bvd Gambetta, 76183 Rouen cedex, France. frederique.caillot@etu.univ-rouen.fr
Telephone: +33-235-148536
Fax: +33-232-888186
Received: August 1, 2008 Revised: November 14, 2008 Accepted: November 21, 2008 Published online: January 21, 2009
Abstract
AIM: 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.
CONCLUSION: 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.
