Predictionofearly-stagehepatocellularcarcinomausingOncoScanchromosomalcopynumberaberrationdata

摘要： AIMToidentifychromosomalcopynumberaberrations(CNAs)inearly-stagehepatocellularcarcinoma(HCC)andanalyzewhethertheyarecorrelatedwithpatientprognosis.METHODSOnehundredandtwentypatientswithearly-stageHCCwereenrolledinourstudy,withthecollectionofformalinfixed,paraffin-embedded(FFPE)specimensandclinicopathologicaldata.Tumorareasweremarkedbycertifiedpathologistsonahematoxylinandeosinstainedslide,andcancerandadjacentnon-canceroustissuesunderwentextractionofDNA,whichwasanalyzedwiththeAffymetrixOncoScanplatformtoassessCNAsandlossofheterozygosity(LOH).Tenindividualswithnonmalignantdiseasewereusedasthecontrolgroup.Anothercohortconsistingof40patientswithstageⅠ/ⅡHCCwereenrolledtoanalyzegeneexpressionandtocorrelatefindingswiththeOncoScandata.RESULTSCopynumberamplificationsoccurredatchromosomes1q21.1-q44and8q12.3-24.3anddeletionswerefoundat4q13.1-q35.2,8p23.2-21.1,16q23.3-24.3,and17p13.3-12,whileLOHcommonlyoccurredat1p32.3,3p21.31,8p23.2-21.1,16q22.1-24.3,and17p13.3-11inearly-stageHCC.UsingCoxregressionanalysis,wealsofoundthatahigherpercentageofgenomechange(≥60%)wasanindependentfactorforworseprognosisinearly-stageHCC(P=0.031).Amongthe875genesintheOncoScanGeneChip,sixwereindependentpredictorsofworsedisease-freesurvival,ofwhichthreewereamplified(MYC,ELAC2,andSYK)andthreeweredeleted(GAK,MECOM,andWRN).Further,patientswithHCCwhoexhibited≥3CNAsinvolvingthesesixgeneshaveworseoutcomescomparedtothosewhohad<3CNAs(P<0.001).Similarly,AsianpatientswithstageIHCCfromTheCancerGenomeAtlasharboringCNAswiththesegeneswerealsopredictedtohavepooreroutcomes.CONCLUSIONPatientswithearly-stageHCCandincreasedgenomechangeorCNAsinvolvingMYC,ELAC2,SYK,GAK,MECOM,orWRNareatriskforpooreroutcomeafterresection. ... （共12頁(yè)）