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

作     者：Céline Derambure Cédric Coulouarn Frédérique Caillot Romain Daveau Martine Hiron Michel Scotte Arnaud Franois Celia Duclos Odile Goria Marie Gueudin Catherine Cavard Benoit Terris Maryvonne Daveau Jean-Philippe Salier 

作者机构：Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les PeptidesFacultéde Médecine-PharmacieRouenFrance Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les PeptidesFacultéde Médecine-PharmacieRouenFrance Service de Chirurgie Générale et DigestiveCentre Hospitalier UniversitaireRouenFrance Département de Pathologie Centre Hospitalier UniversitaireRouenFrance Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les PeptidesFacultéde Médecine-PharmacieRouenFrance Service d'Hépato-gastro-enterologieCentre Hospitalier UniversitaireRouenFrance Laboratoire de Virologie and UPRES EA 2646 Centre Hospitalier UniversitaireRouenFrance Inserm Unité567CNRS UMR 8104 UniversitéParis 5Département GDPMInstitut CochinParis France 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2008年第14卷第11期

页      面：1749-1758页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Grants from ANRS ARC IREB and ConseilRégional de Haute-Normandie to JPS 

主　　题：Alcoholism Chromosome Cirrhosis Hepatitis C Transcriptomes Protein function 

摘      要：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 *** 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 betweenetiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding *** 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(chromo- some preference;differences in transcriptomes and related functions)have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis *** may open novel avenues for differential therapies in this disease.