基于溶質(zhì)載體基因的肝細胞肝癌預后模型的構建與驗證

基于溶質(zhì)載體基因的肝細胞肝癌預后模型的構建與驗證基于溶質(zhì)載體基因的肝細胞肝癌預后模型的構建與驗證

摘要：

肝細胞肝癌是由肝細胞惡性增生導致的癌癥，其發(fā)病率不斷上升。預測肝癌患者的生存期和疾病進展方面存在挑戰(zhàn)。因此，發(fā)現(xiàn)新的肝癌預后因素和構建有效的預后模型非常必要。本研究通過篩選與溶質(zhì)載體基因（SLCO）相關的潛在生物標志物，并基于這些標志物構建了一個肝細胞肝癌預后模型。使用遺傳算法和Kaplan-Meier生存分析法對模型進行了驗證和優(yōu)化。最終，我們成功地建立了一個包含14個變量的肝細胞肝癌預測模型，并在驗證集中得到了良好的驗證結果。研究結果表明，溶質(zhì)載體基因與肝細胞肝癌的發(fā)病、預后密切相關，可以作為預后模型預測因子，提高肝癌患者的生存質(zhì)量和治療效果。

關鍵詞：肝細胞肝癌、預后模型、溶質(zhì)載體基因、生物標志物、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