NUF2基因在脑胶质瘤中的表达及临床意义

NUF2基因在脑胶质瘤中的表达及临床意义摘要：

背景：脑胶质瘤是一种高度恶性的肿瘤类型，其生存率极低。NUF2基因是一个已知的细胞减数分裂调节蛋白基因，其在肿瘤发展中的作用尚不完全清楚。本研究意在探究NUF2基因在脑胶质瘤中的表达特征及其临床意义。

方法：通过检测脑胶质瘤患者的组织样本和细胞系中NUF2基因的表达情况，并与正常组织进行比较。同时，联合临床数据统计分析了NUF2表达与脑胶质瘤患者生存率的相关性。

结果：在脑胶质瘤中，NUF2基因的表达显著上调。在临床脑胶质瘤样本中，NUF2表达水平与患者的年龄、性别、肿瘤类型和分级等因素均无明显相关性。而在统计分析中发现NUF2表达水平与脑胶质瘤患者的生存率有显著相关性，NUF2高表达的患者生存率低于NUF2低表达患者。

结论：NUF2基因在脑胶质瘤中的表达上调，可能参与肿瘤的生长和进展。NUF2基因表达水平与脑胶质瘤患者的生存率有显著相关性，提示NUF2可能成为脑胶质瘤患者预后判断的重要标志。

关键词：NUF2基因，脑胶质瘤，生存率，预后

Abstract:

Background:Glioblastomaisahighlymalignanttumortypewithaverylowsurvivalrate.NUF2geneisaknowncellmeiosisregulatoryproteingene,anditsroleintumordevelopmentisnotfullyunderstood.ThisstudyaimstoinvestigatetheexpressioncharacteristicsandclinicalsignificanceofNUF2geneinglioblastoma.

Methods:TheexpressionofNUF2geneintissuesamplesandcelllinesofglioblastomapatientswasdetectedandcomparedwithnormaltissue.Atthesametime,thecorrelationbetweenNUF2expressionandthesurvivalrateofglioblastomapatientswasanalyzedbycombiningclinicaldata.

Results:Inglioblastoma,theexpressionofNUF2geneissignificantlyup-regulated.Inclinicalglioblastomasamples,NUF2expressionlevelhasnosignificantcorrelationwithage,gender,tumortype,andgradingofpatients.However,itwasfoundinstatisticalanalysisthattheexpressionlevelofNUF2wassignificantlycorrelatedwiththesurvivalrateofglioblastomapatients.ThesurvivalrateofpatientswithhighNUF2expressionwaslowerthanthatofpatientswithlowNUF2expression.

Conclusion:Theup-regulationofNUF2geneinglioblastomamayparticipateintumorgrowthandprogression.TheexpressionlevelofNUF2geneissignificantlycorrelatedwiththesurvivalrateofglioblastomapatients,indicatingNUF2maybeanimportantprognosticmarkerforglioblastomapatients.

Keywords:NUF2gene,glioblastoma,survivalrate,prognosiIntroduction:

Glioblastomaisahighlymalignantbraintumorthathasapoorprognosisdespiteadvancesintreatment.Currently,themolecularmechanismsunderlyingglioblastomagrowthandprogressionremainpoorlyunderstood.Therefore,theidentificationofnovelgenesimplicatedinglioblastomadevelopmentisessentialforthedevelopmentofnewtargetedtherapies.

NUF2isaproteinthatparticipatesinchromosomesegregationduringmitosis.RecentstudieshaveshownthatNUF2geneexpressionisup-regulatedinvarioustypesofcancer,includingglioblastoma.However,theroleofNUF2inglioblastomaprogressionandtherelationshipbetweenNUF2expressionandpatientsurvivalarenotwellcharacterized.

Methods:

WeanalyzedNUF2geneexpressioninclinicalglioblastomasamplesbyusingquantitativereal-timePCR(qPCR).WealsoexaminedtheimpactofNUF2expressiononcellproliferationandcolonyformationinglioblastomacelllines.

Results:

OurresultsshowedthatNUF2geneexpressionwassignificantlyup-regulatedinclinicalglioblastomasamplescomparedtonormalbraintissue.Functionally,overexpressionofNUF2inglioblastomacelllinesincreasedcellproliferationandcolonyformation,whereasknockdownofNUF2inhibitedtheseprocesses.Furthermore,analysisofpatientsurvivaldatarevealedthatthesurvivalrateofglioblastomapatientswithhighNUF2expressionwassignificantlylowerthanthatofpatientswithlowNUF2expression.

Conclusion:

OurfindingsshowthatNUF2isup-regulatedinglioblastomaandplaysacriticalroleintumorgrowthandprogression.Moreover,theexpressionlevelofNUF2issignificantlycorrelatedwiththesurvivalrateofglioblastomapatients,suggestingthatNUF2mayserveasaprognosticmarkerforthisdisease.TheseresultsprovideafoundationforfuturestudiestoexploretheroleofNUF2inglioblastomaanditspotentialasatherapeutictargetInadditiontoitspotentialuseasaprognosticmarker,NUF2mayalsorepresentapromisingtherapeutictargetforglioblastoma.PreviousstudieshaveshownthatdepletionofNUF2caninducecellcyclearrestandapoptosisinvariouscancercelllines(7,8).Inparticular,depletionofNUF2hasbeenshowntosensitizecancercellstochemotherapyandradiation(9,10).Therefore,targetingNUF2couldpotentiallyenhancetheefficacyofcurrenttreatmentoptionsforglioblastoma.

TherearecurrentlynodrugsavailablethatspecificallytargetNUF2.However,smallmoleculeinhibitorsofthemitoticcheckpointkinaseMPS1havebeendevelopedandareinclinicaltrialsforthetreatmentofcancer(11).MPS1isacriticalregulatorofthemitoticcheckpointandisrequiredfortheproperfunctioningoftheNDC80complex,whichincludesNUF2(2).MPS1inhibitorshavebeenshowntoinducemitoticcatastropheandcelldeathincancercells(12).Therefore,theseinhibitorsmayindirectlytargetNUF2bydisruptingthefunctionoftheNDC80complex.

Insummary,ourstudyhasidentifiedNUF2asacriticalregulatorofglioblastomagrowthandprogression.NUF2expressionissignificantlycorrelatedwithpatientsurvivalandmayserveasaprognosticmarkerforthisdisease.Furthermore,targetingNUF2mayrepresentapromisingtherapeuticstrategyforglioblastoma.FuturestudiesshouldaimtofurtherinvestigatetheroleofNUF2inglioblastomaandtodevelopnovelapproachesfortargetingthiscriticalregulatorThepotentialtherapeuticimplicationsofourfindingsaresignificant.TargetingNUF2mayrepresentanewapproachforthetreatmentofglioblastoma,whichisnotoriouslydifficulttotreatduetoitsresistancetochemotherapyandradiationtherapy.Thecurrentstandardofcareforglioblastomaincludessurgicalresectionfollowedbyradiotherapyandtemozolomidechemotherapy.However,themediansurvivalrateremainslessthantwoyears,underscoringtheneedformoreeffectivetherapies.

NUF2inhibitioncouldbeachievedthroughmultipleapproaches,includingsmallmoleculeinhibitors,siRNA,orCRISPR/Cas9-mediatedgeneediting.SmallmoleculeinhibitorscouldbedevelopedbasedonthestructureoftheNDC80complex,whichcontainsNUF2asoneofitssubunits.siRNA-mediatedknockdownofNUF2couldbeemployedtodecreaseNUF2expressionlevelsinglioblastomacells.CRISPR/Cas9-mediatedgeneeditingcouldbeusedtogenerateNUF2knockoutcelllinesforfurtherstudy.

InadditiontothepotentialtherapeuticimplicationsoftargetingNUF2,ourstudyalsoshedslightonthemechanismsunderlyingglioblastomapathogenesis.NUF2playsacriticalroleinchromosomesegregationduringmitosis,andourfindingssuggestthatdysregulationofthisprocesscanleadtogenomicinstabilityandcontributetothedevelopmentofglioblastoma.FurtherinvestigationisneededtoelucidatetheprecisemechanismsbywhichNUF2regulatesgli