Molecular mechanisms of liver carcinogenesis related to metabolic syndrome  

作　　者：Claudia Campani Jean-Charles Nault 

机构地区：[1]Team of Functional Genomics of Solid Tumors,Centre de Recherche des Cordeliers,Sorbonne Université,Inserm,Universitéde Paris,Paris F-75006,France [2]Equipe labellisée Ligue Nationale Contre le Cancer,Labex OncoImmunology,Paris F-75006,France [3]Department of Experimental and Clinical Medicine,University of Florence,Florence 50139,Italy [4]Service d’hépatologie,Hôpital Avicenne,Hôpitaux Universitaires Paris-Seine-Saint-Denis,Assistance-Publique Hôpitaux de Paris,Bobigny 93000,France [5]Unitéde Formation et de Recherche SantéMédecine et Biologie Humaine,UniversitéParis 13,Communautéd’Universités et Etablissements Sorbonne Paris Cité,Bobigny 93000,France

出　　处：《Hepatoma Research》2022年第1期22-34,共13页肝癌研究（英文版）

基　　金：Nault JC received research grant from Bayer and Ipsen.

摘　　要：Global prevalence of non-alcoholic fatty liver disease(NAFLD)and of NAFLD-hepatocellular carcinoma(HCC)is estimated to grow in the next years.The burden of NAFLD and the evidence that NAFLD-HCC arises also in noncirrhotic patients,explain the urgent need of a better characterization of the molecular mechanisms involved in NAFLD progression.Obesity and diabetes cause a chronic inflammatory state which favors changes in serum cytokines and adipokines,an increase in oxidative stress,DNA damage,and the activation of multiple signaling pathways involved in cell proliferation.Moreover,a role in promoting NAFLD-HCC has been highlighted in the innate and adaptive immune system,dysbiosis,and alterations in bile acids metabolism.Several dietary,genetic,or combined mouse models have been used to study nonalcoholic steatohepatitis(NASH)development and its progression to HCC,but models that fully recapitulate the biological and prognostic features of human NASH are still lacking.In humans,four single nucleotide polymorphisms(PNPLA3,TM6SF2,GCKR,and MBOAT7)have been linked to the development of both NASH and HCC in cirrhotic and non-cirrhotic patients,whereas HSD17B13 polymorphism has a protective effect.In addition,higher rates of somatic ACVR2A mutations and a novel mutational signature have been recently discovered in NASH-HCC patients.The knowledge of the molecular pathogenesis of NAFLD-HCC will be helpful to personalized screening programs and allow for primary and secondary chemopreventive treatments for NAFLD patients who are more likely to progress to HCC.

关 键 词：Hepatocellular carcinoma mouse model genetic predisposition CIRRHOSIS non-alcoholic fatty liver disease immune system 

分 类 号：R57[医药卫生—消化系统]