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MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma

World Journal of Gastroenterology 2014年第16期20卷 4723-4729页

作者： Xiang-Fen Ji Yu-Chen Fan Shuai Gao Yang Yang Jian-Jun Zhang Kai Wang Department of Hepatology Qilu Hospital of Shandong University Institute of Hepatology Shandong University

AIM:To investigate the potential of promoter methylation of two tumor suppressor genes(TSGs)as biomarkers for hepatocellular carcinoma(HCC).METHODS:A total of 189 subjects were included in this retrospective cohort,which contained 121 HCC patients without any history of curative treatment,37 patients with chronic hepatitis B(CHB),and 31 normal controls(NCs).DNA samples were extracted from 400μL of serum of each subject and then modified using bisulfite *** of the promoters of the TSGs(metallothionein1M,MT1M;and metallothionein 1G,MT1G)was determined using methylation-specific polymerase chain *** diagnostic value of combined MT1M and MT1G promoter methylation was evaluated using the area under the receiver operating characteristic ***:Our results indicated that the methylation status of serum MT1M(48.8%,59/121)and MT1G(70.2%,85/121)promoters in the HCC group was significantly higher than that in the CHB group(MT1M 5.4%,2/37,P<0.001;MT1G 16.2%,6/37,P<0.001)and NC group(MT1M 6.5%,2/31,P<0.001;MT1G 12.9%,4/27,P<0.001).Aberrant serum MT1M promoter methylation gave higher specificity to discriminate HCC from CHB(94.6%)and NCs(93.5%),whereas combined methylation of serum MT1M and MT1G promoters showed higher diagnostic sensitivity(90.9%),suggesting that they are potential markers for noninvasive detection of ***,MT1M promoter methylation was positively correlated with tumor size(rs=0.321,P<0.001),and HCC patients with both MT1M and MT1G promoter methylation tended to show a higher incidence of vascular invasion or metastasis(P=0.018).CONCLUSION:MT1M and MT1G promoter methylation may be used as serum biomarkers for noninvasive detection of HCC.

关键词： MT1M MT1G Methylation Serum biomarker hepatocellul

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miR-106b-25/miR-17-92 clusters: Polycistrons with oncogenic roles in hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第20期20卷 5962-5972页

作者： Weiqi Tan Yang Li Seng-Gee Lim Theresa MC Tan Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Singapore S117597 Singapore Department of Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore S117597 Singapore

MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational *** polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in *** has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 ***,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 ***-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular *** of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C *** targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and *** this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory *** addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.

关键词： miR-106b-25 cluster miR-17-92 cluster hepatocellul

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Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

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World Journal of Gastroenterology 2014年第40期20卷 14642-14651页

作者： Gianni Testino Patrizia Burra Ferruccio Bonino Francesco Piani Alessandro Sumberaz Roberto Peressutti Andrea Giannelli Castiglione Valentino Patussi Tiziana Fanucchi Ornella Ancarani Giovanna De Cerce Anna Teresa Iannini Giovanni Greco Antonio Mosti Marilena Durante Paola Babocci Mariano Quartini Davide Mioni Sarino Aricò Aniello Baselice Silvia Leone Fabiola Lozer Emanuele Scafato Paolo Borro Regional Alcohologic Centre Liguria Region Alcohol Unit and Related Diseases Department of Internal and Specialist Medicine IRCCS AOU San Martino-IST National Institute for Cancer Research 16100 Genova Italy Gastroenterology Department of Surgical and Gastroenterological Sciences University Hospital of Padova Veneto Region 35100 Padova Italy Internal Medicine University of Pisa 56100 Pisa Italy Department of DependenceASS4 Medio Friuli Regione Autonoma Friuli Venezia Giulia34100 Trieste Italy Regional Transplantation Centre Autonomous Region of Friuli Venezia Giulia 33100 Udine Italy Regional Transplantation Centre Liguria Region 16100 Genova Italy Regional AlcohologicCentre Toscana Region Alcohol Unit Careggi Hospital University of Firenze 50100 Firenze Italy Department of Dependence Molise Region 86100 Campobasso Italy Alcohol Unit Department of Dependence Molise Region 86100 Campobasso Italy Alcohol Unit ASL di Ravenna Emilia Romagna Region 48100 Ravenna Italy Alcohol Unit ASL 4 di Terni Umbria Region05100 Terni Italy Hepatology Unit Santa Maria Hospital 05100 Terni Italy Gastroenterology Ordine Mauriziano Hospital Piemonte Region 10100 Torino Italy Italian Clubs of Alcoholics in Treatment 84134 Salerno Italy Department of Toxicology University of Genova 16100 Genova Italy World Health Organization Collaborating Centre for Research and Health Promotion on Alcohol and Alcohol-related Health Problems Europe Region Istituto Superiore di Sanità 00100 Roma Italy

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis,fibrosis,and cirrhosis to hepatocellular ***-four per cent of all deaths from cirrhosis are attributed to *** liver disease is the second most common diagnosis among patients undergoing liver transplantation(LT).The vast majority of transplant programmes(85%)require 6 mo of abstinence prior to transplantation;commonly referred to as the"6-mo rule".Both in the case of progressive end-stage liver disease(ESLD)and in the case of severe acute alcoholic hepatitis(AAH),not responding to medical therapy,there is a lack of evidence to support a 6-mo sobriety *** is necessary to identify other risk factors that could be associated with the resumption of alcohol ***"Group of Italian Regions"suggests that:in a case of ESLD with model for end-stage liver disease<19 a 6-mo abstinence period is required;in a case of ESLD,a 3-mo sober period before LT may be more ideal than a 6-mo period,in selected patients;and in a case of severe AAH,not respond-ing to medical therapies(up to 70%of patients die within 6 mo),LT is mandatory,even without achieving *** multidisciplinary transplant team must include an addiction specialist/*** have to participate in self-help groups.

关键词： Alcohol Alcoholic hepatitis Cirrhosis hepatocellul

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