Identification of portal vein tumor thrombus with an independent clonal origin in hepatocellular carcinoma via multi-omics data analysis

Objective:Multiplemechanismsunderlyingthedevelopmentofportalveintumorthrombus(PVTT)inhepatocellularcarcinoma(HCC)havebeenreportedrecently.However,theoriginsofPVTTremainunknown.Increasingmulti-omicsdataonPVTTsinHCCshavemadeitpossibletoinvestigatewhetherPVTTsoriginatefromthecorrespondingprimarytumors(Ts).Methods:TheclonalrelationshipbetweenPVTTsandtheircorrespondingprimaryTswasinvestigatedusingdatasetsdepositedinpublicdatabases.OneDNAcopynumbervariationsdatasetandthreegeneexpressiondatasetsweredownloadedfortheanalyses.ClonalityanalysiswasperformedtoinvestigatetheclonalrelationshipbetweenPVTTsandTsfromanindividualpatient.DifferentialgeneexpressionanalysiswasappliedtoinvestigatethegeneexpressionprofilesofPVTTsandTs.Results:Oneoutof19PVTTshadnoclonalrelationshipwithitscorrespondingT,whereastheothersdid.ThePVTTswithindependentclonaloriginshoweddifferentgeneexpressionandenrichmentinbiologicalprocessesfromtheprimaryTs.Basedontheuniquegeneexpressionprofiles,agenesignatureincluding24geneswasusedtoidentifypairsofPVTTsandprimaryTswithoutanyclonalrelationship.ValidationinthreedatasetsshowedthatthesetypesofpairsofPVTTsandTscanbeidentifiedbythe24-genesignature.Conclusions:OurfindingsshowadirectevidenceforPVTToriginandconsolidatetheheterogeneityofPVTTsobservedinclinic.TheresultssuggestthatPVTTinvestigationatamolecularlevelisclinicallynecessaryfordiagnosisandtreatment.