MicroRNA Profile Predicts Recurrence after Resection in Patients with Hepatocellular Carcinoma within the Milan Criteria 英文参考文献.docVIP

MicroRNAProfilePredictsRecurrenceafterResectionin PatientswithHepatocellularCarcinomawithintheMilan Criteria FumiakiSato1*,EtsuroHatano2,KojiKitamura2,AkiraMyomoto3,4,TakeshiFujiwara1 ,Satoko Takizawa3,SokenTsuchiya1,GozohTsujimoto4,ShinjiUemoto2,KazuharuShimizu1 1Department ofNanobioDrug Discovery, Graduate School ofPharmaceutical Sciences,Kyoto University, Kyoto, Japan, 2DepartmentofSurgery,Graduate School of Medicine,KyotoUniversity,Kyoto,Japan,3NewFrontiersResearchLaboratories,TorayIndustries,Inc.Kanagawa,Japan,4DepartmentofPharmacogenomics,Graduate SchoolofPharmaceuticalSciences,KyotoUniversity,Kyoto,Japan Abstract Objective: Hepatocellular carcinoma (HCC) is difficult to manage due to the high frequency of post-surgical recurrence. Early detection of the HCC recurrence after liver resection is important in making further therapeutic options, such as salvagelivertransplantation.Inthisstudy,weutilizedmicroRNAexpressionprofilingtoassesstheriskofHCCrecurrence afterliverresection. Methods:WeexaminedmicroRNAexpressionprofilinginpairedtumorandnon-tumorlivertissuesfrom73HCCpatients whosatisfiedtheMilanCriteria.Weconstructedpredictionmodelsofrecurrence-freesurvivalusingtheCoxproportional hazard model and principal component analysis. The prediction efficiency was assessed by the leave-one-out cross- validationmethod,andthetime-averagedareaundertheROCcurve(ta-AUROC). Results:TheunivariateCoxanalysisidentified13and56recurrence-relatedmicroRNAsinthetumorandnon-tumortissues, suchasmiR-96.Thenumberofrecurrence-relatedmicroRNAswassignificantlylargerinthenon-tumor-derivedmicroRNAs (N-miRs)thaninthetumor-derivedmicroRNAs(T-miRs,P,0.0001).Thebestta-AUROCusingthewholedataset,T-miRs,N- miRs, and clinicopathological dataset were 0.8281, 0.7530, 0.7152, and 0.6835, respectively. The recurrence-free survival curveofthelow-riskgroupstratifiedbythebestmodelwassignificantlybetterthanthatofthehigh-riskgroup(Log-rank: P=0.00029).TheT-miRstendtopredictearlyrecurrencebetterthanlaterecur