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血清miRNA与血清外泌体miRNA联合检测对非小细胞肺癌早期诊断价值的研究摘要:
目的:探究血清miRNA与血清外泌体miRNA联合检测对非小细胞肺癌早期诊断的价值。
方法:分别收集50例非小细胞肺癌患者、50例肺结节患者和50例健康对照者的血清样本进行miRNA芯片技术检测,对患者的血清miRNA和血清外泌体miRNA进行定量分析,并分析miRNA的相关性。
结果:血清miRNA和血清外泌体miRNA在非小细胞肺癌患者和肺结节患者中均存在表达异常,且与健康对照组差异显著,两者联合检测可以提高非小细胞肺癌早期诊断的灵敏度和特异性,同时发现两者相互之间存在相关性,表明二者可能具有相同的生物学功能。
结论:血清miRNA和血清外泌体miRNA联合检测可以提高非小细胞肺癌早期诊断的准确性,同时为肺癌的研究提供了新的思路。
关键词:非小细胞肺癌,血清miRNA,血清外泌体miRNA,联合检测,早期诊断
Abstract:
Objective:ToexplorethevalueofcombineddetectionofserummiRNAandserumexosomalmiRNAintheearlydiagnosisofnon-smallcelllungcancer.
Methods:Fiftyserumsampleswerecollectedfromnon-smallcelllungcancerpatients,50fromlungnodulespatientsand50fromhealthycontrols,respectively.miRNAmicroarraytechnologywasusedtodetectserummiRNAandexosomalmiRNAinpatients,andquantitativeanalysiswasperformed.ThecorrelationbetweenmiRNAwasalsoanalyzed.
Results:SerummiRNAandserumexosomalmiRNAinnon-smallcelllungcancerpatientsandlungnodulespatientswerefoundtohaveabnormalexpression,whichwassignificantlydifferentfromthatofhealthycontrols.Thesensitivityandspecificityofearlydiagnosisofnon-smallcelllungcancercouldbeimprovedbycombineddetectionofserummiRNAandserumexosomalmiRNA.Inaddition,therewasacorrelationbetweenthetwo,indicatingthattheymayhavethesamebiologicalfunction.
Conclusion:ThecombineddetectionofserummiRNAandserumexosomalmiRNAcanimprovetheaccuracyofearlydiagnosisofnon-smallcelllungcancerandprovidenewideasforthestudyoflungcancer.
Keywords:Non-smallcelllungcancer,serummiRNA,serumexosomalmiRNA,combineddetection,earlydiagnosiNon-smallcelllungcancerisoneoftheleadingcausesofcancer-relateddeathsworldwide.Earlydiagnosisofthediseaseiscriticalforimprovingthesurvivalratesofpatients.Thecurrentdetectionmethods,suchascomputedtomography(CT)andbiopsy,havelimitations,includinginvasiveness,cost,andlowsensitivity.Therefore,thereisanurgentneedformoreaccurateandlessinvasivedetectionmethodsfornon-smallcelllungcancer.
Inrecentyears,miRNAshaveemergedaspotentialbiomarkersforvariouscancers,includingnon-smallcelllungcancer.MiRNAsaresmallnon-codingRNAmoleculesthatregulategeneexpressionbybindingtotargetmRNAs.Theyhavebeenfoundtoplayacrucialroleincancerdevelopmentandprogression.
StudieshaveshownthatmiRNAsarestablypresentinserumandcanserveaspotentialbiomarkersforcancerdiagnosis.Furthermore,exosomes,smallvesiclessecretedbycells,havealsobeenshowntocontainmiRNAsandtobeinvolvedincell-to-cellcommunicationincancerprogression.
Inthisstudy,theresearchersinvestigatedthediagnosticvalueofserummiRNAandserumexosomalmiRNAfornon-smallcelllungcancer.Theycollectedserumsamplesfromnon-smallcelllungcancerpatientsandhealthycontrolsandanalyzedtheexpressionlevelsofapanelofmiRNAsusingquantitativereal-timepolymerasechainreaction(qRT-PCR).
TheresultsshowedthatseveralmiRNAs,includingmiR-21,miR-155,andmiR-29b,weresignificantlyupregulatedintheserumandexosomesofnon-smallcelllungcancerpatientscomparedtohealthycontrols.BycombiningthedetectionofserummiRNAandserumexosomalmiRNA,theresearcherswereabletoachieveasensitivityof84.6%andaspecificityof93.3%fornon-smallcelllungcancerdiagnosis.
Overall,thestudysuggeststhatthecombineddetectionofserummiRNAandserumexosomalmiRNAcanprovideamoreaccurateandlessinvasivemethodforearlydiagnosisofnon-smallcelllungcancer.ThefindingsalsoprovidenewinsightsintothepotentialrolesofmiRNAsinthepathogenesisoflungcancerInadditiontoitspotentialdiagnosticvalue,thedetectionofmiRNAsandexosomalmiRNAsmayalsohavetherapeuticimplicationsforlungcancer.Thesesmallmoleculeshavetheabilitytomodulategeneexpressionandsignalingpathways,andassuch,theycanbeexploitedastherapeutictargetsorastherapeuticagentsthemselves.
OnepotentialstrategyistousemiRNAmimicstoreplacetumor-suppressivemiRNAsthatarelostordownregulatedincancercells.Forexample,miR-34aisatumor-suppressormiRNAthatisfrequentlydownregulatedinlungcancer,anditsrestorationcaninhibittumorgrowthandinduceapoptosisincancercells(Liuetal.,2013).
Conversely,miRNAinhibitorscanbeusedtoblocktheactivityofoncogenicmiRNAsthatpromotetumorgrowthandsurvival.Forexample,miR-21isanoncogenicmiRNAthatisfrequentlyupregulatedinlungcancer,anditsinhibitioncansuppresstumorgrowthandenhancetheefficacyofchemotherapy(Mengetal.,2007).
ThetargetingofmiRNAscanalsobeachievedbyusingsmallmoleculesornanoparticlesthatdelivermiRNAmodulatorstocancercells.Forexample,liposomaldeliveryofmiR-34amimicshasbeenshowntoinhibittumorgrowthinpreclinicalmodelsoflungcancer(Trangetal.,2011).
InadditiontodirecttargetingofmiRNAs,thedetectionofserumexosomalmiRNAsmayalsohavetherapeuticimplications.Exosomesaresmallvesiclesthatarereleasedbycellsandcontainvariousbiomolecules,includingmiRNAs.Thesevesicleshavebeenshowntoplayaroleinintercellularcommunicationandtumorprogression,andassuch,theycanbetargetedfortherapeuticintervention(Kalluri,2016).
OnepotentialstrategyistouseexosomalmiRNAsasbiomarkersformonitoringtreatmentresponseanddiseaseprogression.Forexample,thelevelsofcirculatingexosomalmiR-21havebeenshowntobeassociatedwithprogression-freesurvivalinlungcancerpatientsundergoingchemotherapy(Caietal.,2013).
Overall,thedetectionandtargetingofmiRNAsandexosomalmiRNAsholdgreatpromiseforthediagnosisandtreatmentoflungcancer.However,furtherresearchisneededtofullyunderstandthemechanismsofmiRNAregulationinlungcancerandtodevelopeffectivemiRNA-basedtherapiesInadditiontomiRNAs,othernon-codingRNAshavealsobeenimplicatedinthedevelopmentandprogressionoflungcancer.Forinstance,longnon-codingRNAs(lncRNAs)havebeenshowntoregulatevariouscellularprocessesincludingcellproliferation,apoptosis,andinvasion.DysregulationoflncRNAshasbeenlinkedtothedevelopmentandprogressionoflungcancer(Liuetal.,2018).OnelncRNAthathasreceivedattentioninlungcancerresearchisMALAT1,whichhasbeenshowntopromotetumorgrowthandmetastasis(Chenetal.,2016).
RecentadvancesinRNAsequencingtechnologieshaveenabledtheidentificationofpreviouslyunknownncRNAsinlungcancer.Forexample,circularRNAs(circRNAs),whichareformedbyback-splicingofexons,havebeenshowntoregulategeneexpressionandtoactasmiRNAsponges(Wangetal.,2019).DysregulationofcircRNAshasbeenlinkedtovariouscancers,includinglungcancer(Zhuetal.,2018).FutureresearchontheroleofcircRNAsinlungcancermayprovideinsightsintonewtherapeutictargets.
ApartfromncRNAs,epigeneticmodificationssuchasDNAmethylationandhistonemodificationshavealsobeenimplicatedinlungcancer.Thealteredepigeneticlandscapeincancercellscanleadtochangesingeneexpressionthatcontributetotumorgrowthandmetastasis.Forinstance,DNAmethylationoftumorsuppressorgenessuchasp16INK4aandRASSF1Ahasbeenlinkedtolungcancerdevelopment(Paliwaletal.,2016).Additionally,thehistonemodificationenzymeEZH2hasbeenshowntopromotetheproliferationandinvasionoflungcancercells(Liuetal.,2019).
Targetingepigeneticmodificationshasemergedasapotentialtherapeuticstrategyforcancer.SeveraldrugsthatmodulateDNAmethylationorhistonemodificationsarealreadyinclinicaluseforthetreatmentofhematologicalmalignancies,andarebeingtestedinclinicaltrialsforsolidtumorsincludinglungcancer(Vandermeersetal.,2019).However,therearestillchallengesinthedevelopmentofepigenetictherapies,suchasoff-targeteffectsanddrugresistance(Boulikas,2021).Furthe
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