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 Franois Celia Duclos Odile Goria Marie Gueudin Catherine Cavard Benoit Terris Maryvonne Daveau Jean-Philippe Salier 

机构地区：[1]Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides,Facultéde Médecine-Pharmacie,Rouen,France [2]Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides,Facultéde Médecine-Pharmacie,Rouen,France Service de Chirurgie Générale et Digestive,Centre Hospitalier Universitaire,Rouen,France [3]Département de Pathologie, Centre Hospitalier Universitaire,Rouen,France [4]Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides,Facultéde Médecine-Pharmacie,Rouen,France Service d'Hépato-gastro-enterologie,Centre Hospitalier Universitaire,Rouen,France [5]Laboratoire de Virologie and UPRES EA 2646, Centre Hospitalier Universitaire,Rouen,France [6]Inserm Unité567,CNRS UMR 8104, UniversitéParis 5,Département GDPM,Institut Cochin,Paris, France

出　　处：《World Journal of Gastroenterology》2008年第11期1749-1758,共10页世界胃肠病学杂志（英文版）

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

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 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 betweenetiologies 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(chromo- some 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.AIM： To look at a comprehensive picture of etiologydependent 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.

关 键 词：ALCOHOLISM CHROMOSOME CIRRHOSIS Hepatitis C TRANSCRIPTOMES Protein function 

分 类 号：R735.7[医药卫生—肿瘤]