基于溶質(zhì)載體基因的肝細(xì)胞肝癌預(yù)后模型的構(gòu)建與驗(yàn)證

基于溶質(zhì)載體基因的肝細(xì)胞肝癌預(yù)后模型的構(gòu)建與驗(yàn)證基于溶質(zhì)載體基因的肝細(xì)胞肝癌預(yù)后模型的構(gòu)建與驗(yàn)證

摘要：

肝細(xì)胞肝癌是由肝細(xì)胞惡性增生導(dǎo)致的癌癥，其發(fā)病率不斷上升。預(yù)測肝癌患者的生存期和疾病進(jìn)展方面存在挑戰(zhàn)。因此，發(fā)現(xiàn)新的肝癌預(yù)后因素和構(gòu)建有效的預(yù)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(guān)的潛在生物標(biāo)志物，并基于這些標(biāo)志物構(gòu)建了一個(gè)肝細(xì)胞肝癌預(yù)后模型。使用遺傳算法和Kaplan-Meier生存分析法對(duì)模型進(jìn)行了驗(yàn)證和優(yōu)化。最終，我們成功地建立了一個(gè)包含14個(gè)變量的肝細(xì)胞肝癌預(yù)測模型，并在驗(yàn)證集中得到了良好的驗(yàn)證結(jié)果。研究結(jié)果表明，溶質(zhì)載體基因與肝細(xì)胞肝癌的發(fā)病、預(yù)后密切相關(guān)，可以作為預(yù)后模型預(yù)測因子，提高肝癌患者的生存質(zhì)量和治療效果。

關(guān)鍵詞：肝細(xì)胞肝癌、預(yù)后模型、溶質(zhì)載體基因、生物標(biāo)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