miR-320a、ANGPTL2与VEGF在NSCLC中的表达及临床意义

miR-320a、ANGPTL2与VEGF在NSCLC中的表达及临床意义摘要：目的：研究miR-320a、ANGPTL2与VEGF在NSCLC组织中的表达及其与肿瘤临床病理参数之间的关系，探讨其在NSCLC的诊断和治疗中的临床意义。方法：采用实时荧光定量PCR和免疫组织化学的方法检测NSCLC组织中miR-320a、ANGPTL2和VEGF的表达，并分析其与临床病理参数之间的关系。结果：miR-320a在NSCLC组织中显著降低，而ANGPTL2和VEGF显著升高。miR-320a的表达与肿瘤大小、分化程度、淋巴结转移和TNM分期相关，ANGPTL2和VEGF的表达与分化程度、淋巴结转移和TNM分期相关。miR-320a的低表达和ANGPTL2、VEGF的高表达与NSCLC患者的预后不良相关。结论：miR-320a、ANGPTL2和VEGF在NSCLC中的异常表达与肿瘤的恶性程度密切相关，可以用作NSCLC的早期诊断和预后评估的生物标志物，并为NSCLC的治疗提供新的靶点和策略。

关键词：miR-320a；ANGPTL2；VEGF；NSCLC；临床意义

Introduction

非小细胞肺癌（NSCLC）是最常见的肺癌类型，具有高度异质性和恶性程度，其预后仍然较差。因此，研究NSCLC发生和发展的机制及寻找新的治疗靶点具有重要的临床意义。

Methods

本研究采用实时荧光定量PCR和免疫组织化学的方法检测NSCLC组织中miR-320a、ANGPTL2和VEGF的表达，并分析其与临床病理参数之间的关系。

Results

miR-320a在NSCLC组织中显著降低，而ANGPTL2和VEGF显著升高。miR-320a的表达与肿瘤大小、分化程度、淋巴结转移和TNM分期相关，ANGPTL2和VEGF的表达与分化程度、淋巴结转移和TNM分期相关。miR-320a的低表达和ANGPTL2、VEGF的高表达与NSCLC患者的预后不良相关。

Conclusion

miR-320a、ANGPTL2和VEGF在NSCLC中的异常表达与肿瘤的恶性程度密切相关，可以用作NSCLC的早期诊断和预后评估的生物标志物，并为NSCLC的治疗提供新的靶点和策略。

Keywords:miR-320a,ANGPTL2,VEGF,NSCLC,clinicalsignificance。Non-smallcelllungcancer(NSCLC)isthemostcommontypeoflungcancerandishighlyheterogeneousandmalignant,withapoorprognosis.Therefore,studyingthemechanismsunderlyingNSCLCdevelopmentandidentifyingnewtherapeutictargetsisofgreatclinicalsignificance.

Inthisstudy,real-timequantitativePCRandimmunohistochemistrywereusedtodetecttheexpressionofmiR-320a,ANGPTL2,andVEGFinNSCLCtissueandanalyzetheirrelationshipwithclinicalandpathologicalparameters.

TheresultsshowedthatmiR-320awassignificantlydownregulatedinNSCLCtissue,whileANGPTL2andVEGFweresignificantlyupregulated.TheexpressionofmiR-320awascorrelatedwithtumorsize,differentiationdegree,lymphnodemetastasis,andTNMstaging,whiletheexpressionofANGPTL2andVEGFwascorrelatedwithdifferentiationdegree,lymphnodemetastasis,andTNMstaging.LowexpressionofmiR-320aandhighexpressionofANGPTL2andVEGFwereassociatedwithapoorprognosisinNSCLCpatients.

Inconclusion,theabnormalexpressionofmiR-320a,ANGPTL2,andVEGFiscloselyrelatedtothemalignantdegreeofNSCLCandcanbeusedasabiomarkerforearlydiagnosisandprognosisevaluation.TheyalsoprovidenewtargetsandstrategiesforthetreatmentofNSCLC。Apartfromtheabove-mentionedbiomarkers,severalotherpotentialbiomarkershavealsobeenresearchedforNSCLC.Forinstance,theexpressionofcirculatingtumorcells(CTCs)andtheirsubtypes,aswellasexosomalbiomarkers,haveshownpromisingresultsinNSCLCdiagnosis,prognosis,andtreatmentmonitoring.CTCsandexosomescontainvaluableinformationaboutthetumor,suchasDNAmutations,proteinexpressions,andmiRNAprofiles,thusprovidinganon-invasiveandmorecomprehensiveapproachtocancerdiagnosisandpatientmanagement.

Moreover,severalimmune-relatedbiomarkers,suchasprogrammeddeath-ligand1(PD-L1),tumor-infiltratinglymphocytes(TILs),andcytokines,havebeenidentifiedascriticaldeterminantsofNSCLCimmunotherapyresponse.PD-L1expressionontumorcellsandTILsinfiltrationintothetumormicroenvironmenthavebeencorrelatedwithimprovedresponsetoimmunecheckpointblockadetherapy.Furthermore,thecytokineprofileofNSCLCpatients,particularlytheinterleukin(IL)-6,-8,and-10,hasalsobeenlinkedtocancerprogression,immuneescape,andtherapeuticresistance.

Intheeraofprecisionmedicine,theidentificationofaccurateandreliableNSCLCbiomarkersthatcanpredicttreatmentresponseandpatientoutcomesremainsacrucialchallenge.Thus,furtherresearchisneededtovalidatetheexistingbiomarkersanddiscovernewonestotailorpersonalizedtreatmentsforNSCLCpatients.Additionally,thedevelopmentofnoveldiagnostictoolsandtechniques,suchasliquidbiopsiesandimagingmodalities,mayfacilitateearlydetectionandmonitoringofNSCLC,therebyimprovingpatientsurvivalandqualityoflife。Besidesbiomarkersanddiagnostictools,otherareasofresearchthatcouldpotentiallyimprovetheoutcomesofNSCLCpatientsincludeadvancingtargetedtherapies,immunotherapies,andcombinationtherapies.

Targetedtherapiessuchastyrosinekinaseinhibitors(TKIs)andmonoclonalantibodieshaveshownpromisingresultsintreatingNSCLCpatientswhosetumorsharborspecificgeneticmutationsoroverexpresscertainproteins.Forexample,theuseofTKIssuchaserlotinib,gefitinib,andafatinibhastransformedthetreatmentlandscapeforEGFR-mutantNSCLC,leadingtoimprovedresponserates,progression-freesurvival,andoverallsurvival.Similarly,monoclonalantibodiessuchasbevacizumabandramucirumabthattargetthevascularendothelialgrowthfactor(VEGF)pathwayhavedemonstratedefficacyinimprovingsurvivaloutcomesinpatientswithadvancedNSCLC.

Immunotherapies,particularlyimmunecheckpointinhibitorstargetingtheprogrammeddeath-1(PD-1)andprogrammeddeathligand-1(PD-L1)pathways,haverevolutionizedthetreatmentofNSCLCinrecentyears.Theseagentsstimulatethepatient'sownimmunesystemtoattackcancercells,resultingindurableresponsesandimprovedsurvivaloutcomes.Approximately25-30%ofNSCLCpatientsexpresshighlevelsofPD-L1,andthesepatientshaveshownthegreatestbenefitfromPD-1/PD-L1inhibitorssuchaspembrolizumab,nivolumab,andatezolizumab.However,asignificantproportionofPD-L1-negativeand/orlow-expressingpatientsalsoderivesomebenefitfromtheseagents,highlightingtheneedformorereliablebiomarkerstopredictresponse.

CombinationtherapiesthattargetmultiplepathwayssimultaneouslyarealsobeinginvestigatedtoovercomeresistancemechanismsandimproveefficacyinNSCLC.Forexample,thecombinationofchemotherapyandimmunotherapyhasshownpromisingresultsinseveralphaseIIItrials,leadingtoFDAapprovalsforpembrolizumabpluschemotherapyandatezolizumabplusbevacizumabinthefirst-linesettingforNSCLC.Similarly,thecombinationofTKIsandimmunotherapiesisbeingevaluatedinongoingclinicaltrials,withearlydatasuggestingimprovedresponseratesandsurvivaloutcomes.

Insummary,NSCLCremainsachallengingdiseasewithsignificantmorbidityandmortalityworldwide.Althoughthedevelopmentoftargetedtherapies,immunotherapies,andcombinationtherapieshasimprovedoutcomesformanypatients,thereisstillaneedformorereliablebiomarkersanddiagnostictoolstoguidetreatmentdecisions,aswellasongoingresearchtoaddressresistancemechanismsandimproveefficacy.Withtheseefforts,thehopeistoeventuallyachievepersonalized,precisionmedicineforallNSCLCpatientsinthefuture。Furthermore,itisessentialtorecognizetheroleofmultidisciplinarycareinthemanagementofNSCLC.Ateamapproachinvolvingsurgeons,medicalandradiationoncologists,pulmonologists,pathologists,andnursescanensurethatpatientsreceivecomprehensive,individualizedcarethroughouttheirjourney.Thisapproachnotonlyimprovesoutcomesbutalsoenhancespatientsatisfactionandqualityoflife.

Moreover,lungcancerscreeningprogramshaveemergedasacrucialstrategyfortheearlydetectionoflungcancer,particularlyforthoseathighrisk.Low-dosecomputedtomography(LDCT)screeningisnowrecommendedforindividualsaged55-80yearswhohavea30-pack-yearsmokinghistoryandcurrentlysmokeorquitwithinthepast15years.LDCTscreeninghasbeenshowntoreducemortalityfromlungcancerby20%,aswellastheincidenceoflate-stagediagnosis.

Despiterecentprogress,disparitiesinlungcanceroutcomesstillexist.Individualsfromdisadvantagedbackgrounds,ethnicminorities,andruralpopulationshaveahigherincidenceoflungcancer,lowerratesofscreeningandaccesstocare,andworseoutcomes.Addressingthesedisparitiesrequiresamultifacetedapproach,includingcommunity-basededucationandoutreach,policychanges,andincreasedaccesstoscreeningandtreatment.

Insummary,NSCLCremainsasignificantpublichealthissueworldwide,andongoingeffortsareneededtoimproveoutcomesforpatients.Advancesinresearch,thedevelopmentoftargetedtherapies,andmultidisciplinarycareareessentialcomponentsinachievingpersonalized,precisionmedicineforallNSCLCpatients.Additionally,theimplementationoflungcancerscreeningprogramsandaddressingdisparitiesinoutcomeswillhelpreducetheburdenofthisdevastatingdisease。Furthermore,earlydetectionanddiagnosisofNSCLCareparamountinimprovingoutcomesforpatients.Lungcancerscreeningprogramsusinglow-doseCTscanshavebeenshowntoreducemortalityratesbydetectingearlystagelungcancer.However,screeningprogramsareoftenunderutilizedanddisparitiesinaccessanduptakeexist.Strategiestoimprovescreeningratesinhigh-riskpopulations,includingeducationandoutreachefforts,mayhelpreducedisparitiesandimproveoutcomesforpatients.

Inaddition,addressingdisparitiesinoutcomesforNSCLCpatientsiscrucial.Lungcancerincidenceandmortalityratesarehigheramongcertainpopulations,includingminoritiesandlow-incomeindividuals,highlightingtheimportanceofaddressingsocialdeterminantsofhealth.Accesstoqualityhealthcareandresources,includingtimelydiagnosisandtreatment,canimpactoutcomesforNSCLCpatients.Addressingtheseinequitiesthroughpoliciesandstrategiesmayhelpreducetheburdenoflungcanceronthesevulnerablepopulations.

Inconclusion,NSCLCremainsasignificantglobalhealthissuewithpooroutcomesformanypatients.Advancesinresearchandtreatment,alongwithmultidisciplinarycare,personalizedandprecisionmedicine,andlungcancerscreeningprogramsareessentialinimprovingoutcomesforNSCLCpatients.Furthermore,addressingdisparitiesinaccesstocareandoutcomesisanecessarycomponentofreducingtheburdenofthisdevastatingdiseaseonvulnerablepopulations.OngoingeffortsareneededtoadvancestrategiesthatreducetheimpactofNSCLCandimproveoutcomesforallpatients。Inadditiontotheeffortsmentionedabove,thereareseveralotherareaswhereprogresscanbemadeinimprovingoutcomesforNSCLCpatients.Oneareaoffocusisthedevelopmentofnewandinnovativetherapies.Despiterecentadvances,NSCLCremainsachallengingdiseasetotreat,particularlyinpatientswhohaveadvancedormetastaticdisease.Therefore,thereisaneedforcontinuedresearchintonewtreatmentsthattargetspecificmolecularpathwaysorimmunecheckpointsintumors.

PrecisionmedicinealsoholdsgreatpromiseforNSCLCpatients.Thisapproachinvolvesusingmolecularprofilingtoidentifythespecificgeneticmutationsdrivingapatient'stumorandthentargetingthosemutationswithspecifictherapies.Thisstrategycanleadtomoreeffectivetreatmentswithfewersideeffectsforpatients.Inrecentyears,severalnewtargetedtherapieshavebeenapprovedforNSCLC,andongoingresearchisexploringnewwaystoutilizeprecisionmedicinetoimproveoutcomes.

MultidisciplinarycareisanotheressentialcomponentofimprovingoutcomesforNSCLCpatients.Thisapproachinvolvesateamofspecialistsfromdifferentdisciplinesworkingtogethertodevelopacomprehensivetreatmentplanforeachpatient.Amultidisciplinarycareteammayincludemedicaloncologists,radiationoncologists,surgeons,pulmonologists,andotherhealthcareprofessionals.Byworkingcollaboratively,thesespecialistscanensurethatpatientsreceivethemosteffectivetreatmentsfortheirspecificdiseaseandthattheircareiscoordinatedandwell-managed.

LungcancerscreeningprogramsalsoplayacriticalroleinimprovingoutcomesforNSCLCpatients.Byidentifyinglungcanceratanearlystage,patientshaveamuchgreaterchanceofbeingsuccessfullytreatedandsurvivingthedisease.Severallarge-scalescreeningtrialshaveshownthatlow-doseCTscanscandetectearly-stagelungcancerinhigh-riskindividuals,leadingtoearlierdiagnosisandimprovedoutcomes.Therefore,ongoingeffortsareneededtoexpandaccesstolungcancerscreeningprogramsforthoseathighriskforthedisease.

Lastly,addressingdisparitiesinaccesstocareandoutcomesisacrucialcomponentofreducingtheburden