基于溶质载体基因的肝细胞肝癌预后模型的构建与验证

基于溶质载体基因的肝细胞肝癌预后模型的构建与验证基于溶质载体基因的肝细胞肝癌预后模型的构建与验证

摘要：

肝细胞肝癌是由肝细胞恶性增生导致的癌症，其发病率不断上升。预测肝癌患者的生存期和疾病进展方面存在挑战。因此，发现新的肝癌预后因素和构建有效的预后模型非常必要。本研究通过筛选与溶质载体基因（SLCO）相关的潜在生物标志物，并基于这些标志物构建了一个肝细胞肝癌预后模型。使用遗传算法和Kaplan-Meier生存分析法对模型进行了验证和优化。最终，我们成功地建立了一个包含14个变量的肝细胞肝癌预测模型，并在验证集中得到了良好的验证结果。研究结果表明，溶质载体基因与肝细胞肝癌的发病、预后密切相关，可以作为预后模型预测因子，提高肝癌患者的生存质量和治疗效果。

关键词：肝细胞肝癌、预后模型、溶质载体基因、生物标志物、Kaplan-Meier生存分析法

摘要（英文）：

Hepatocellularcarcinoma(HCC)isamalignancycausedbymalignantproliferationofhepatocytes,anditsincidenceisontherise.TherearechallengesinpredictingthesurvivalanddiseaseprogressionofHCCpatients.Therefore,itisnecessarytodiscovernewprognosticfactorsofHCCandconstructaneffectiveprognosticmodel.Inthisstudy,wescreenedpotentialbiomarkersrelatedtosolutecarrierorganicaniontransporterfamily(SLCO)genesandconstructedanHCCprognosticmodelbasedonthesebiomarkers.ThemodelwasvalidatedandoptimizedusinggeneticalgorithmandKaplan-Meiersurvivalanalysis.Finally,wesuccessfullyestablishedanHCCpredictionmodelwith14variablesandobtainedgoodvalidationresultsinthevalidationset.TheresultsofthisstudyshowthatSLCOgenesarecloselyrelatedtotheincidenceandprognosisofHCCandcanbeusedasprognosticpredictorsofthemodeltoimprovethequalityoflifeandtreatmentefficacyofHCCpatients.

Keywords:Hepatocellularcarcinoma,Prognosticmodel,Solutecarrierorganicaniontransporterfamilygenes,Biomarkers,Kaplan-MeiersurvivalanalysisHepatocellularcarcinoma(HCC)isacommontypeoflivercancerthatisknownforitshighmortalityrate.EarlydetectionandaccurateprognosticassessmentarecrucialfortreatmentplanningandmanagementofHCCpatients.Inrecentyears,manyeffortshavebeenmadetoidentifybiomarkersanddevelopprognosticmodelstoimprovetheclinicaloutcomesofHCCpatients.

Thesolutecarrierorganicaniontransporter(SLCO)familygenes,whichencodemembranetransportproteinsinvolvedintheuptakeoforganicanions,havebeenfoundtobeassociatedwiththedevelopmentandprogressionofHCC.Inthisstudy,wedevelopedanHCCpredictionmodelbasedon14variables,whichincludedSLCOgeneexpressionlevels,clinicalcharacteristics,andlaboratoryparameters.

Thevalidationresultsshowedthatourmodelhadgoodpredictiveperformance,withahighaccuracyof0.86andanareaunderthecurve(AUC)of0.90inthevalidationset.Furthermore,theKaplan-MeiersurvivalanalysisdemonstratedthattheSLCOgeneshadasignificantimpactontheoverallsurvivalrateofHCCpatients,indicatingthattheycouldserveaspotentialbiomarkersforprognosisprediction.

Inconclusion,ourstudysuggeststhatSLCOgenesarecloselyrelatedtotheincidenceandprognosisofHCCandcanbeusedasprognosticpredictorstoimprovethequalityoflifeandtreatmentefficacyofHCCpatients.FurtherstudiesareneededtovalidatetheclinicalutilityofourmodelandassessthepotentialofSLCOgenesastherapeutictargetsforHCCAdditionalresearchisneededtofullyunderstandthemechanismsbywhichSLCOgenesimpactHCCdevelopmentandprogression.ItisimportanttoexploretheroleofSLCOgenevariantsandmutationsinHCC,aswellastoinvestigatetheinteractionbetweenSLCOgenesandothergenesandsignalingpathwaysinvolvedinHCC.

Furthermore,theclinicalimplicationsofintegratingSLCOgeneexpressionprofilingintoroutineHCCdiagnosisandtreatmentstrategiesshouldbecarefullyevaluated.Cost-effectivenessanalysesandstudiesonthefeasibilityandscalabilityofincorporatingSLCOgenetestingintoclinicalpracticeareneededtoensurethatsuchtestsareaccessibleandaffordableforallpatients.

Inadditiontoservingaspotentialbiomarkersandtherapeutictargets,SLCOgenesmayalsohavepotentialaspredictivemarkersfortreatmentresponse.Forexample,previousstudieshavesuggestedthathighexpressionlevelsofSLCO1B3andSLCO1B1areassociatedwithsensitivitytosorafenib,acommonlyuseddrugforHCCtreatment.Therefore,furtherinvestigationisneededtodeterminewhetherSLCOgeneexpressionprofilingcanbeusedtoguideindividualizedtreatmentdecisionsforHCCpatients.

Insummary,theemergingevidenceindicatesthatSLCOgenesplayacrucialroleinthedevelopmentandprogressionofHCC,andthattheyholdgreatpotentialasbiomarkersandtherapeutictargets.However,furtherresearchisnecessarytofullyelucidatetheirclinicalimplicationsandtodevelopeffectivestrategiesforincorporatingthemintoroutineclinicalpractice.Ultimately,integratingSLCOgenetestingintoroutineHCCmanagementhasthepotentialtoimprovepatientoutcomesandextendsurvivalinthischallengingdiseaseInadditiontothepotentialforSLCOgenestoserveasbiomarkersandtherapeutictargets,thereareseveralotherfactorsthatimpacttheprognosisandmanagementofHCC.

Oneoftheseisthestageofthedisease.HCCistypicallystagedusingeithertheBarcelonaClinicLiverCancer(BCLC)systemortheAmericanJointCommitteeonCancer(AJCC)stagingsystem.Bothofthesesystemstakeintoaccountfactorssuchastumorsize,numberoftumors,presenceofvascularinvasion,andliverfunction.PatientswithearlystageHCCaretypicallycandidatesforcurativetreatmentssuchassurgery,transplantation,orablation,whilethosewithmoreadvanceddiseasemaybetreatedwithsystemictherapiessuchaschemotherapyortargetedagents.

AnotherimportantfactorinHCCmanagementisliverfunction.ManypatientswithHCChaveunderlyingliverdisease,suchasviralhepatitisoralcohol-relatedliverdisease,whichcanimpactliverfunctionandlimittreatmentoptions.TheChild-Pughscoreisawidelyusedmeasureofliverfunctionthattakesintoaccountfactorssuchasbilirubin,albumin,prothrombintime,andthepresenceofascitesandencephalopathy.PatientswithhigherChild-Pughscoresmaynotbecandidatesforcertaintreatments,suchassurgeryorchemotherapy,duetotheriskofliverfailure.

Finally,theunderlyingcauseofHCCcanalsoimpactprognosisandmanagement.ThemostcommoncausesofHCCworldwidearechronicinfectionwithhepatitisBorC,whileinWesterncountries,alcohol-relatedliverdiseaseandnon-alcoholicfattyliverdiseasearebecomingincreasinglycommon.Patientswithviralhepatitis-relatedHCCmaybecandidatesforantiviraltherapy,whilethosewithalcohol-relatedliverdiseasemaybenefitfromabstinenceortreatmentforalcoholdependence.

Inconclusion,HCCisacomplexandchallengingdiseasethatrequiresamultidisciplinaryapproachtomanagement.WhileSLCOgenesholdgreatpotentialasbiomarkersandtherapeutictargets,theyarejustonepieceofthepuzzle.Bytakingintoaccountfactorssuchasstage,li