Objective:Hepatocellularcarcinoma(HCC)isacommonmalignancyassociatedwithhighmorbidityandmortalityratesworldwide.EarlydiagnosisplaysanimportantroleintheimprovementofHCCprognosis.Methods:Inthisstudy,weconductedacomprehensiveanalysisofHCCDNAmethylationandgeneexpressiondatasetsinTheCancerGenomeAtlas(TCGA),toidentifyaprognosticsignatureforHCCdiagnosisandsurvivalprediction.First,weidentifieddifferentialmethylationCpG(dmCpG)sitesinHCCsamplesandcomparedthemwiththoseinadjacentnormallivertissues;thiswasfollowedbyunivariateanalysisandSureIndependenceScreening(SIS)inthetrainingset.Therobustnessoftheidentifiedprognosticsignaturewasevaluatedusingthetestingset.ToexplorethebiologicalprocessesinvolvedinHCCprogression,wealsoperformedfunctionalenrichmentanalysisforoverlappinggenesbetweengenescontainingdmCpGsites(DMGs)anddifferentialexpressiongenes(DEGs)inHCCpatients,usingdatafromtheDatabaseforAnnotation,Visualization,andIntegratedDiscovery(DAVID).Results:Asaresult,weidentifiedfiveCpGsitesthatweresignificantlyassociatedwithHCCsurvivalthroughunivariateanalysisandSIS.Univariateanalysisofclinicalcharacteristicsidentifiedageandriskfactors(includingalcoholconsumptionandsmoking)asindependentfactorsthatindicatedHCCsurvival.Multivariateanalysisindicatedthattheintegratedprognosticsignature(weightedcombinationofthefiveCpGsites)thattookageandriskfactorsintoconsiderationresultedinmoreaccuratesurvivalprediction.Conclusions:ThisstudyprovidesanovelsignatureforpredictingHCCsurvival,andshouldbehelpfulforearlyHCCdiagnosisandpersonalizedtreatment.
