HEPATOBILIARYMALIGNANCIESLongNoncodingRNAAssociatedWithMicrovascularInvasioninHepatocellularCarcinomaPromotesAngiogenesisandServesasaPredictorforHepatocellularCarcinomaPatients’PoorRecurrence-FreeSurvivalAfterHepatectomySheng-XianYuan,1*FuYang,2*YuanYang,1Qi-FeiTao,1JinZhang,1GangHuang,1YunYang,1Ruo-YuWang,1SenYang,1Xi-SongHuo,2LingZhang,2FangWang,2Shu-HanSun,2andWei-PingZhou1Survivalofpatientswithhepatocellularcarcinoma(HCC)remainspoor,whichislargelyattributedtoactiveangiogenesis.However,themechanismsunderlyingangiogenesisinHCCremaintobediscovered.Inthisstudy,wefoundthatlongnoncodingRNAassoci-atedwithmicrovascularinvasioninHCC(lncRNAMVIH)(lncRNAassociatedwithmi-crovascularinvasioninHCC)wasgenerallyoverexpressedinHCC.Inacohortof215HCCpatients,theoverexpressionofMVIHwasassociatedwithfrequentmicrovascularinvasion(P50.016)andahighertumornodemetastasisstage(P50.009)aswellasdecreasedrecurrence-freesurvival(RFS)(P<0.001)andoverallsurvival(P50.007).Moreover,theup-regulationofMVIHservedasanindependentriskfactortopredictpoorRFS.WealsofoundthatMVIHcouldpromotetumorgrowthandintrahepaticmetastasisbyactivatingangiogenesisinmousemodels.SubsequentinvestigationsindicatedthatMVIHcouldactivatetumor-inducingangiogenesisbyinhibitingthesecretionofphospho-glyceratekinase1(PGK1).Additionally,in65HCCsamples,MVIHexpressionwasinver-selycorrelatedwiththeserumlevelofPGK1andpositivelycorrelatedwiththemicrovesseldensity.Conclusion:DeregulationoflncRNAMVIHisapredictorforpoorRFSofHCCpatientsafterhepatectomyandcouldbeutilizedasapotentialtargetfornewadjuvanttherapiesagainstactiveangiogenesis.(HEPATOLOGY2012;56:2231-2241)Hepatocellularcarcinoma(HCC)iscurrentlythefifth-mostcommonsolidtumorworld-wideandthesecondleadingcauseofcancer-relateddeathsinChina.1,2Althoughremarkablepro-gresshasbeenmadeinrecentdecades,thedetailsofthemolecularmechanismsunderlyingHCCcarcino-genesisremaintobeelucidated.2,3SurvivalofpatientswithHCChasbeenimprovedwithadvancementsinsurgicaltechniques,butthemediansurvivalrateremain...
