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

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