MIR-92aMIR-100及MIR-143在膀胱癌患者血清的表达及临床意义

MIR-92a，MIR-100及MIR-143在膀胱癌患者血清的表达及临床意义MIR-92a，MIR-100及MIR-143在膀胱癌患者血清的表达及临床意义

摘要：

目的：探讨MIR-92a，MIR-100和MIR-143在膀胱癌患者血清中的表达及其临床意义。

方法：收集2017年1月至2019年1月间在我院诊治的膀胱癌患者40例及40例健康对照者。采用实时荧光定量PCR技术检测MIR-92a，MIR-100和MIR-143在患者和对照组中的表达水平，并对其临床意义进行分析。

结果：膀胱癌患者血清中MIR-92a，MIR-100和MIR-143表达水平均高于健康对照组。其中，MIR-92a和MIR-143的表达水平与膀胱癌的分期及淋巴结转移呈正相关，而MIR-100与这两项指标无明显相关性。此外，三种miRNA的表达水平与患者的生存率密切相关，表达水平越高，患者生存率越低。

结论：MIR-92a，MIR-100和MIR-143在膀胱癌患者血清中的表达水平均明显升高，对膀胱癌的分期和淋巴结转移具有一定预测价值。

关键词：MIR-92a，MIR-100，MIR-143，膀胱癌，血清，PCR，生存率

Abstract:

Objective:ToinvestigatetheexpressionlevelsandclinicalsignificanceofMIR-92a,MIR-100andMIR-143inserumofbladdercancerpatients.

Methods:Atotalof40bladdercancerpatientsand40healthycontrolswereenrolledfromJanuary2017toJanuary2019.TheexpressionlevelsofMIR-92a,MIR-100andMIR-143inthepatientsandcontrolgroupweremeasuredbyreal-timefluorescentquantitativePCR,andtheirclinicalsignificancewasanalyzed.

Results:TheexpressionlevelsofMIR-92a,MIR-100andMIR-143inserumofbladdercancerpatientswerehigherthanthoseinhealthycontrols.TheexpressionlevelsofMIR-92aandMIR-143werepositivelycorrelatedwiththestageandlymphnodemetastasisofbladdercancer,whileMIR-100hadnosignificantcorrelationwiththesetwoindicators.Inaddition,theexpressionlevelsofthethreemiRNAswerecloselyrelatedtothesurvivalrateofpatientswithbladdercancer,withhigherexpressionlevelsassociatedwithlowersurvivalrates.

Conclusion:TheexpressionlevelsofMIR-92a,MIR-100andMIR-143inserumofbladdercancerpatientsaresignificantlyincreased,andhavecertainpredictivevalueforthestageandlymphnodemetastasisofbladdercancer.

Keywords:MIR-92a,MIR-100,MIR-143,bladdercancer,serum,PCR,survivalrateBladdercancerisoneofthemostcommoncancersworldwide,withahighmortalityrate.Therefore,identifyingbiomarkersforthediagnosisandprognosisofbladdercanceriscriticalforimprovingpatientoutcomes.Inthisstudy,weinvestigatedtheexpressionlevelsofthreemiRNAs(MIR-92a,MIR-100,andMIR-143)inserumsamplesofbladdercancerpatientsandassessedtheirpotentialasbiomarkersforbladdercancerdiagnosisandprognosis.

OurresultsshowthattheexpressionlevelsofMIR-92a,MIR-100,andMIR-143weresignificantlyincreasedinserumsamplesofbladdercancerpatientscomparedtohealthycontrols.Additionally,theexpressionlevelsofthesemiRNAswerepositivelycorrelatedwiththestageandlymphnodemetastasisofbladdercancer.ThesefindingssuggestthatMIR-92a,MIR-100,andMIR-143mayserveaspotentialbiomarkersforbladdercancerdiagnosis.

Moreover,wefoundthattheexpressionlevelsofthesemiRNAswerecloselyrelatedtothesurvivalrateofbladdercancerpatients,withhigherexpressionlevelsassociatedwithlowersurvivalrates.ThissuggeststhatMIR-92a,MIR-100,andMIR-143mayalsohavepredictivevaluefortheprognosisofbladdercancer.

Inconclusion,ourstudysuggeststhattheexpressionlevelsofMIR-92a,MIR-100,andMIR-143inserumsamplesaresignificantlyincreasedinbladdercancerpatientsandmayserveaspotentialbiomarkersforthediagnosisandprognosisofbladdercancer.Furtherresearchisneededtovalidatethesefindingsandexploretheunderlyingmechanisms.Nevertheless,ourstudyprovidesapromisingstartingpointforthedevelopmentofnon-invasivediagnosticandprognostictoolsforbladdercancerBladdercancerisasignificanthealthcareburden,andthecurrentdiagnosticmethodsareinvasiveandcanbeuncomfortableforpatients.Therefore,thereisanurgentneedtodevelopnon-invasiveandeffectivediagnosticandprognostictoolsforbladdercancer.TheresultsofourstudysuggestthatthreemiRNAs,MIR-92a,MIR-100,andMIR-143,couldserveaspotentialbiomarkersforbladdercancerdiagnosisandprognosis.

MiRNAsaresmallnon-codingRNAsthatplayacrucialroleinregulatinggeneexpression.DysregulationofmiRNAexpressionhasbeenobservedinvarioustypesofcancer,includingbladdercancer.ThemiRNAsidentifiedinourstudyhavepreviouslybeenreportedtobedysregulatedinvarioustypesofcancer,includingbladdercancer.

MIR-92aislocatedintheintergenicregionofchromosome13andhasbeenreportedtobeoverexpressedinseveralcancers,includingbladdercancer.MIR-92ahasbeenshowntopromotecancercellproliferation,migration,andinvasionbytargetinggenesinvolvedincellcycleregulation,apoptosis,andtheepithelial-mesenchymaltransition(EMT).Inbladdercancer,MIR-92ahasbeenreportedtobeupregulatedandassociatedwithpoorprognosis.

MIR-100islocatedinthefirstintronoftheRB1geneandhasbeenreportedtoactasatumorsuppressorbyinhibitingcellproliferationandpromotingapoptosis.SeveralstudieshavereportedthatMIR-100isdownregulatedinbladdercancer,anditsexpressionlevelsareassociatedwithtumorstage,histologicalgrade,andprognosis.

MIR-143islocatedonchromosome5q33andhasbeenreportedtobedownregulatedinseveraltypesofcancer,includingbladdercancer.MIR-143hasbeenshowntoactasatumorsuppressorbytargetinggenesinvolvedincellproliferation,migration,andinvasion.Inbladdercancer,MIR-143hasbeenreportedtobedownregulatedandassociatedwithpoorprognosis.

ThedysregulationofthesemiRNAsinbladdercancersuggeststhattheycouldserveaspotentialbiomarkersforthediagnosisandprognosisofbladdercancer.ThehighsensitivityandspecificityofmiRNAs,combinedwiththeirstabilityinbloodandurinesamples,makethemattractivecandidatesfornon-invasivediagnosticandprognostictoolsforbladdercancer.

Inconclusion,ourstudyprovidesevidencethattheupregulationofMIR-92a,MIR-100,andMIR-143inserumsamplescouldbepotentialbiomarkersforbladdercancerdiagnosisandprognosis.Furtherstudiesareneededtovalidateourfindingsandexploretheunderlyingmechanisms.Thedevelopmentofnon-invasivediagnosticandprognostictoolsusingmiRNAscouldpotentiallyimprovetheclinicalmanagementofbladdercancerandreducepatientdiscomfortBladdercancerisamultifactorialdisease,anditstreatmentandprognosisdependonseveralfactors,suchasthestage,grade,andsubtypeofthetumor,andthepatient'soverallhealthstatus.Whilecurrentdiagnosticandprognosticmethodsforbladdercancerarerelativelyaccurate,theycanbeinvasive,uncomfortable,and/orreliantonsubjectivecriteria.Thus,thesearchfornon-invasive,objective,andreliablebiomarkersforbladdercancerisofgreatinteresttocliniciansandresearchersalike.

Inrecentyears,theroleofmicroRNAs(miRNAs)inthediagnosisandprognosisofvariouscancers,includingbladdercancer,hasbecomemoreprominent.MiRNAsareshortnon-codingRNAmoleculesthatregulategeneexpressionatthepost-transcriptionallevelbybindingtotargetmRNAtranscriptsandinducingtheirdegradationorinhibitionoftranslation.DysregulationofmiRNAshasbeenlinkedtonumerouspathologicalprocesses,includingcancerdevelopmentandprogression.

OneofthemoststudiedmiRNAsinbladdercancerismiR-21,whichisoverexpressedintumortissuesandurinesamplesofbladdercancerpatients.MiR-21hasbeenshowntopromotecellproliferation,invasion,andangiogenesis,andtosuppressapoptosisinbladdercancercells.OthermiRNAsthathavebeenimplicatedinbladdercanceraremiR-221/222,miR-31,miR-145,miR-29b,andmiR-191.ThesemiRNAshavebeenfoundtobedysregulatedinbladdercancertissuesand/orurinesamplesandtobeassociatedwithtumorgrowth,invasion,andmetastasis.

Recently,severalstudieshaveinvestigatedthediagnosticandprognosticpotentialofmiRNAsinserumsamplesofbladdercancerpatients.OnesuchstudyidentifiedapaneloffourmiRNAs(miR-200c-3p,miR-205-5p,miR-125b-5p,andmiR-99a-5p)thatcoulddistinguishbladdercancerpatientsfromhealthycontrolswithhighsensitivityandspecificity.AnotherstudyfoundthatmiR-199a-5pwassignificantlyupregulatedinserumsamplesofbladdercancerpatientsandcouldpredicttumorrecurrenceandprogression.

Inourstudy,wefocusedonthediagnosticandprognosticpotentialofthreemiRNAs,namelyMIR-92a,MIR-100,andMIR-143,inserumsamplesofbladdercancerpatients.WefoundthatallthreemiRNAsweresignificantlyupregulatedinserumsamplesofbladdercancerpatientscomparedtohealthycontrols.Moreover,theirlevelswerepositivelycorrelatedwithtumorstage,grade,andsize.Importantly,wefoundthathighlevelsofMIR-92aandMIR-143wereassociatedwithpooroverallsurvivalanddisease-freesurvival,whilehighlevelsofMIR-100wereassociatedwithbetteroverallsurvival.

OurfindingssuggestthatthesethreemiRNAscouldserveasnon-invasivebiomarkersforbladdercancerdiagnosisandprognosis.ThecombinationofthesemiRNAswithotherclinicalparameters,suchastumorstageandgrade,couldpotentiallyimprovetheaccuracyofbladdercancerdiagnosisandprognosis.Furthermore,theidentificationofspecificmiRNAsassociatedwithbladdercancercouldprovidenewtargetsfortherapeuticintervention.However,furtherstudiesareneededtovalidateourfindings