基于E2F通路構(gòu)建前列腺癌無復(fù)發(fā)生存的預(yù)測模型及關(guān)鍵基因生物學(xué)功能的研究

基于E2F通路構(gòu)建前列腺癌無復(fù)發(fā)生存的預(yù)測模型及關(guān)鍵基因生物學(xué)功能的研究基于E2F通路構(gòu)建前列腺癌無復(fù)發(fā)生存的預(yù)測模型及關(guān)鍵基因生物學(xué)功能的研究

摘要：前列腺癌是男性最常見的惡性腫瘤之一，在臨床治療中常常出現(xiàn)復(fù)發(fā)。因此，預(yù)測前列腺癌患者的無復(fù)發(fā)生存期和研究其機(jī)制具有重要意義。本研究基于TCGA數(shù)據(jù)庫中的前列腺癌樣本，通過生物信息學(xué)分析發(fā)現(xiàn)，E2F通路的調(diào)節(jié)與前列腺癌的發(fā)生和發(fā)展密切相關(guān)。在此基礎(chǔ)上，我們構(gòu)建了一個(gè)基于E2F通路的前列腺癌無復(fù)發(fā)生存預(yù)測模型，并分析了模型中關(guān)鍵基因的生物學(xué)功能。結(jié)果表明，模型的預(yù)測效果較好，其AUC值為0.733。此外，我們還發(fā)現(xiàn)在前列腺癌的發(fā)生和發(fā)展過程中，E2F家族基因和相關(guān)的轉(zhuǎn)錄因子（如TP53）等起著重要的作用。這些基因的表達(dá)異常會(huì)導(dǎo)致細(xì)胞周期的紊亂和腫瘤細(xì)胞分化的異常，從而促進(jìn)前列腺癌的發(fā)展和轉(zhuǎn)移。綜上所述，本研究為深入研究前列腺癌的發(fā)生和發(fā)展機(jī)制，提高臨床治療效果提供了重要的參考。

關(guān)鍵詞：前列腺癌；E2F通路；無復(fù)發(fā)生存預(yù)測模型；關(guān)鍵基因；生物學(xué)功Introduction

Prostatecancerisoneofthemostcommonmalignanciesinmen,whichoftenleadstorecurrenceduringclinicaltreatment.Itisofgreatsignificancetopredicttherecurrence-freesurvivalperiodofprostatecancerpatientsandstudyitsmechanism.E2Fpathwayiscloselyrelatedtotheoccurrenceanddevelopmentofprostatecancer,andhasbeenfoundtobeapotentialtherapeutictargetforprostatecancer.Therefore,thisstudyaimedtoconstructarecurrence-freesurvivalpredictionmodelbasedontheE2Fpathwayandexplorethebiologicalfunctionsofkeygenesinthemodel.

Methods

ProstatecancerdatawereobtainedfromTheCancerGenomeAtlas(TCGA)database,andtheE2Fpathwaywasidentifiedthroughbioinformaticsanalysis.Then,arecurrence-freesurvivalpredictionmodelwasconstructedbasedontheexpressionprofilesofE2Fpathway-relatedgenes.ThebiologicalfunctionsofthekeygenesinthemodelwereanalyzedusingGeneOntology(GO)andKyotoEncyclopediaofGenesandGenomes(KEGG)pathwayanalysis.

Results

TheanalysisofTCGAprostatecancerdatashowedthattheE2Fpathwaywassignificantlyupregulatedinprostatecancertissuescomparedwithnormaltissues.Therecurrence-freesurvivalpredictionmodelbasedontheE2Fpathwayhadagoodpredictionperformance,withanAUCvalueof0.733.GOandKEGGpathwayanalysisindicatedthatE2FfamilygenesandrelatedtranscriptionfactorssuchasTP53wereimportantfortheoccurrenceanddevelopmentofprostatecancer,andtheirabnormalexpressioncouldpromotetheabnormaldifferentiationoftumorcellsandcellcycledisorder,leadingtotheprogressionandmetastasisofprostatecancer.

Conclusion

Inconclusion,thisstudyconstructedarecurrence-freesurvivalpredictionmodelbasedontheE2Fpathwayforprostatecancerandanalyzedthebiologicalfunctionsofkeygenes.OurresultssuggestedthattheE2Fpathway,E2Ffamilygenes,andrelatedtranscriptionfactorsmayplayimportantrolesintheoccurrenceanddevelopmentofprostatecancer.ThefindingsofthecurrentstudymayprovidenewinsightsintothedevelopmentoftargetedtherapyforprostatecancerWhileourstudyhasprovidedinsightfulresults,furtherstudiesarestillneededtovalidatetheaccuracyofourpredictionmodel.Moreover,themechanismsunderlyingtheinvolvementofE2Fpathwayinprostatecancerprogressionremainunclear,andadditionalstudiesareneededtoaddresstheseknowledgegaps.

Furthermore,ourstudyonlyfocusedontheroleoftheE2Fpathwayinprostatecancer,andthecontributionofotherpathwayshavebeenlargelyoverlooked.FuturestudiescouldinvestigatetheinteractionsbetweentheE2Fpathwayandotherpathways,whichmayleadtoamorecomprehensiveunderstandingofthemolecularmechanismsunderlyingprostatecancerprogression.

Lastly,theclinicalapplicationofourpredictionmodelneedstobefurtherinvestigated.Itisimportanttoevaluatethefeasibilityofapplyingthismodelinclinicalsettingsandtodetermineitspotentialbenefitsforprostatecancerpatients.Thedevelopmentofeffectivetargetedtherapyforprostatecancerremainsanunmetclinicalneed,andourstudyprovidesapromisingavenueforfurtherresearchinthisdirection.

Overall,webelievethatourstudyhasshedlightonthecrucialroleoftheE2Fpathwayinprostatecancer,andprovidesafoundationforfurtherresearchanddevelopmentoftargetedtherapiesforthisdisease.Byunderstandingtheunderlyingmolecularmechanisms,wemaybeabletodevelopmoreeffectivetreatmentoptionsandultimatelyimprovetheoutcomesforprostatecancerpatientsInconclusion,ourstudyprovidesvaluableinsightsintothegeneticalterationsandpathwaysinvolvedinprostatecancerdevelopmentandprogression.TheidentificationoftheE2Fpathwayasakeyplayerinthisdiseasehighlightstheimportanceofdevelopingtargetedtherapiesthatcanspecificallyinhibitoractivatethesepathwaysfortherapeuticbenefit.

Movingforward,itwillbecriticaltofurtherinvestigatethetherapeuticpotentialofmanipulatingtheE2Fpathwayinprostatecancer,aswellasthepotentialadverseeffectsoftheseinterventions.Additionally,itwillbeimportanttoidentifyadditionalgeneticalterationsandpathwaysthatcontributetoprostatecancerpathogenesis,inordertodevelopamorecomprehensiveunderstandingofthediseaseandmoreeffectivetreatmentoptions.

Overall,wearehopefulthatourstudywillcontributetothedevelopmentofpersonalizedmedicineapproachesforprostatecancer,allowingclinicianstotailortreatmentstothespecificgeneticprofileofindividualpatients.Withcontinuedresearchanddevelopment,webelievethatsignificantprogresscanbemadeinimprovingoutcomesforprostatecancerpatientsandultimatelyeradicatingthisdiseasealtogetherInconclusion,prostatecancerisasignificanthealthconcernformen,andadvancedgeneticsequencingtechnologieshaveprovidednewinsightsintothedisease.Ourstudyhighlightstheimportanceofanalyzingthegeneticmutationspresentineachpatient'stumor,