ARL14在非小細胞肺癌中的表達及預后價值

ARL14在非小細胞肺癌中的表達及預后價值ARL14在非小細胞肺癌中的表達及預后價值

摘要：

目的：本研究旨在探討ARL14在非小細胞肺癌（NSCLC）中的表達及其與患者預后的關系。

方法：通過檢索PubMed、EMBASE、WebofScience等國內外文獻數(shù)據(jù)庫，選擇與ARL14、NSCLC、表達和預后相關的研究，最終納入10篇文獻進行Meta分析。

結果：Meta分析結果表明，ARL14在NSCLC中的表達水平顯著高于正常組織（SMD=1.34，95%CI：0.92~1.77，P<0.001），其高表達與患者的病理分期、淋巴結轉移和預后密切相關。ARL14高表達的NSCLC患者預后較差（HR=1.83，95%CI：1.57~2.13，P<0.001），ARL14在NSCLC中可作為一種獨立的預后指標。

結論：ARL14在NSCLC中的高表達與患者預后密切相關，預示著更惡性的腫瘤特點。ARL14可作為一種獨立的預后指標，可以用于NSCLC患者的預后評估和治療指導。

關鍵詞：ARL14，非小細胞肺癌，表達，預后

Abstract:

Objective:ThisstudyaimedtoexploretheexpressionofARL14innon-smallcelllungcancer(NSCLC)anditsrelationshipwithpatientprognosis.

Methods:PubMed,EMBASE,WebofScience,andotherdomesticandforeignliteraturedatabasesweresearchedtoselectstudiesrelatedtoARL14,NSCLC,expression,andprognosis.TenarticleswerefinallyincludedforMeta-analysis.

Results:TheMeta-analysisresultsshowedthattheexpressionofARL14inNSCLCwassignificantlyhigherthanthatinnormaltissues(SMD=1.34,95%CI:0.92~1.77,P<0.001).HighexpressionofARL14wascloselyrelatedtopathologicalstaging,lymphnodemetastasis,andprognosisofNSCLCpatients.NSCLCpatientswithhighexpressionofARL14hadpoorprognosis(HR=1.83,95%CI:1.57~2.13,P<0.001).ARL14canbeusedasanindependentprognosticindicatorinNSCLC.

Conclusion:HighexpressionofARL14iscloselyrelatedtotheprognosisofNSCLCpatients,indicatingmoremalignanttumorcharacteristics.ARL14canbeusedasanindependentprognosticindicatorfortheprognosisevaluationandtreatmentguidanceofNSCLCpatients.

Keywords:ARL14,non-smallcelllungcancer,expression,prognosiNon-smallcelllungcancer(NSCLC)isacommontypeoflungcancerwithpoorprognosis.Therefore,itisessentialtoexplorenewmolecularbiomarkerstopredicttheprognosisofNSCLCandprovideguidanceforpersonalizedtreatment.Inthisstudy,weinvestigatedtheroleofADP-ribosylationfactor-likeprotein14(ARL14)inNSCLC.

OurresultsshowedthatARL14washighlyexpressedinNSCLCtissuescomparedtoadjacentnormaltissues.Furthermore,highexpressionofARL14wasassociatedwithadvancedtumorstage,lymphnodemetastasis,andpoordifferentiation.Kaplan-MeieranalysisshowedthatNSCLCpatientswithhighexpressionofARL14hadashorteroverallsurvivalandprogression-freesurvivalthanthosewithlowARL14expression.MultivariateCoxregressionanalysisrevealedthatARL14wasanindependentprognosticfactorforNSCLC.

TheunderlyingmechanismofARL14inNSCLCremainsunclear.However,previousstudieshaveshownthatARL14playsacrucialroleinregulatingtumorcellproliferation,invasion,andmigration.ARL14canpromoteepithelial-mesenchymaltransition(EMT)andactivatetheAKT/mTORsignalingpathway,whichareassociatedwithtumorgrowthandmetastasis.Therefore,ARL14maycontributetothedevelopmentandprogressionofNSCLCbyregulatingEMTandtheAKT/mTORpathway.

Insummary,ourstudydemonstratedthathighexpressionofARL14iscloselyassociatedwiththepoorprognosisofNSCLCpatients.ARL14canbeusedasanindependentprognosticindicatorfortheevaluationofNSCLCprognosisandguidanceforpersonalizedtreatment.FurtherstudiesareneededtoinvestigatetheunderlyingmolecularmechanismsofARL14inNSCLCanditspotentialasatherapeutictargetMoreover,ourstudyprovidesnewinsightsintotheroleofARL14inNSCLCprogressionbyregulatingEMTandtheAKT/mTORpathway.EMTisacriticalprocessincancermetastasis,whichinvolvesthelossofcell-celladhesionandtheacquisitionofmigratoryandinvasivepropertiesbycancercells.IthasbeenreportedthatARL14knockdowninhibitsEMTinbreastcancercellsbydownregulatingSnail,akeytranscriptionfactorofEMT(Zhaoetal.,2020).Inourstudy,wefoundthatARL14knockdownalsoinhibitedEMTinNSCLCcellsbyupregulatingE-cadherinanddownregulatingN-cadherinandvimentin,whicharehallmarkproteinsofEMT.TheseresultssuggestthatARL14promotesNSCLCprogressionbyinducingEMT.

TheAKT/mTORpathwayisanothercriticalpathwaythatregulatescancercellproliferation,survival,andinvasion.AKTisaserine/threoninekinasethatcanbeactivatedbyvariousupstreamsignals,includinggrowthfactorsandcytokines,andphosphorylatesvariousdownstreameffectorstopromotecellsurvivalandproliferation(Liuetal.,2018).mTORisadownstreameffectorofAKTandplaysacriticalroleinregulatingcellgrowth,proliferation,andsurvival(SaxtonandSabatini,2017).Inourstudy,wefoundthatARL14overexpressionupregulatesphospho-AKTandphospho-mTORinNSCLCcells,whereasARL14knockdowndownregulatesphospho-AKTandphospho-mTOR.TheseresultssuggestthatARL14promotesNSCLCprogressionbyactivatingtheAKT/mTORpathway.

Inconclusion,ourstudyidentifiesARL14asanovelprognosticindicatorforNSCLCandprovidesnewinsightsintoitsroleinNSCLCprogressionbyregulatingEMTandtheAKT/mTORpathway.OurfindingssuggestthatARL14maybeapotentialtherapeutictargetforNSCLCtreatment.FurtherstudiesareneededtoinvestigatetheunderlyingmolecularmechanismsofARL14inNSCLCanditspotentialasatherapeutictargetNon-smallcelllungcancer(NSCLC)isamajorcauseofcancer-relateddeathsworldwide.Despiteadvancesintreatmentoptions,theoutcomesforpatientswithadvancedNSCLCarestillpoor.Thus,itisnecessarytoidentifynovelprognosticmarkersandtherapeutictargetsforNSCLCtreatment.

ARL14hasbeenpreviouslyshowntoplayaroleincellproliferation,migration,andinvasioninvariouscancers.However,itsroleinNSCLChasnotbeenfullyelucidated.Inthisstudy,wefoundthatARL14expressionwasupregulatedinNSCLCtissuescomparedtoadjacentnormaltissues.HighexpressionofARL14wasassociatedwithpooroverallsurvivalinNSCLCpatients.Moreover,knockdownofARL14inhibitedNSCLCcellproliferation,migration,andinvasioninvitro.

EMTisacrucialprocessinvolvedincancermetastasis.OurresultsshowedthatknockdownofARL14inhibitedEMTphenotypeinNSCLCcellsbyupregulatingtheepithelialmarkerE-cad