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结直肠癌组织中Twist、E-cadherin、β-catenin表达及其临床病理意义摘要:目的:研究结直肠癌组织中Twist、E-cadherin、β-catenin表达及其临床病理意义。方法:收集100例经手术切除结直肠癌患者的癌组织,采用免疫组织化学方法检测Twist、E-cadherin、β-catenin的表达情况,并对其与患者临床病理资料进行统计学分析。结果:100例结直肠癌组织中Twist、E-cadherin、β-catenin的表达量均高于正常组织;Twist和β-catenin的高表达与患者的TNM分期、淋巴结转移及预后密切相关;E-cadherin的低表达也预示着患者的淋巴结转移和预后不良。结论:Twist和β-catenin的高表达以及E-cadherin的低表达与结直肠癌的发病、恶化以及预后密切相关,可为临床治疗提供重要参考依据。
关键词:Twist、E-cadherin、β-catenin、结直肠癌、免疫组织化学
Abstract:Objective:ToinvestigatetheexpressionofTwist,E-cadherin,andβ-cateninincolorectalcancertissueanditsclinicalpathologicalsignificance.Methods:Colorectalcancertissueswerecollectedfrom100patientswhounderwentsurgicalresection,andtheexpressionofTwist,E-cadherin,andβ-cateninwasdetectedbyimmunohistochemistry.Theclinicalpathologicaldataofthepatientswerestatisticallyanalyzed.Results:TheexpressionofTwist,E-cadherin,andβ-cateninin100casesofcolorectalcancertissueswashigherthanthatinnormaltissues.HighexpressionofTwistandβ-cateninwascloselyrelatedtoTNMstaging,lymphnodemetastasis,andprognosisofpatients.LowexpressionofE-cadherinalsoindicatedlymphnodemetastasisandpoorprognosisofpatients.Conclusion:HighexpressionofTwistandβ-cateninandlowexpressionofE-cadherinarecloselyrelatedtotheoccurrence,deterioration,andprognosisofcolorectalcancer,whichcanprovideimportantreferenceforclinicaltreatment.
Keywords:Twist,E-cadherin,β-catenin,colorectalcancer,immunohistochemistryColorectalcancerisacommonmalignancywithhighmorbidityandmortalityrates.Theoccurrenceanddevelopmentofcolorectalcancerarecloselyrelatedtothechangesintheexpressionofvariousmolecularmarkers.Twist,β-catenin,andE-cadherinarecrucialmolecularmarkersinvolvedintheoccurrenceandprogressionofcolorectalcancer.
Twistisatranscriptionalregulatorthatplaysavitalroleintheprocessofepithelial-mesenchymaltransition(EMT),whichpromotestumorinvasionandmetastasis.Inthisstudy,highexpressionofTwistwasdetectedincolorectalcancertissues,whilelowexpressionofTwistwasobservedinadjacentnormaltissues.ThissuggeststhatTwistiscloselyrelatedtotheoccurrenceanddevelopmentofcolorectalcancer.Moreover,highTwistexpressionwasassociatedwithadvancedTNMstaging,lymphnodemetastasis,andpoorprognosisofpatients.
β-CateninisakeytranscriptionalactivatoroftheWntsignalingpathway,whichplaysacriticalroleinregulatingcellproliferation,differentiation,andapoptosis.Inthisstudy,highexpressionofβ-cateninwasdetectedincolorectalcancertissues,whilelowexpressionofβ-cateninwasobservedinadjacentnormaltissues.Thissuggeststhatβ-cateniniscloselyrelatedtotheoccurrenceanddevelopmentofcolorectalcancer.Moreover,highβ-cateninexpressionwasassociatedwithadvancedTNMstaging,lymphnodemetastasis,andpoorprognosisofpatients.
E-cadherinisanimportantcelladhesionmoleculethatregulatescell-celladhesion,migration,andinvasion.Inthisstudy,lowexpressionofE-cadherinwasdetectedincolorectalcancertissues,whilehighexpressionofE-cadherinwasobservedinadjacentnormaltissues.ThissuggeststhatE-cadheriniscloselyrelatedtotheoccurrenceanddevelopmentofcolorectalcancer.Moreover,lowE-cadherinexpressionwasassociatedwithlymphnodemetastasisandpoorprognosisofpatients.
Insummary,highexpressionofTwistandβ-cateninandlowexpressionofE-cadherinarecloselyrelatedtotheoccurrence,deterioration,andprognosisofcolorectalcancer.Thesemolecularmarkerscouldserveaspotentialtargetsforthedevelopmentofeffectivetherapiesforcolorectalcancer.ThefindingsofthisstudyprovideimportantreferencefortheclinicaltreatmentofcolorectalcancerOtherpotentialmolecularmarkersthathavebeenimplicatedinthedevelopmentandprogressionofcolorectalcancerincludemicroRNAs,longnoncodingRNAs,andtumor-associatedantigens.MicroRNAsareshortnoncodingRNAsthatplayacriticalroleintheregulationofgeneexpression.DysregulationofmicroRNAshasbeenlinkedtothedevelopmentandprogressionofvariouscancers,includingcolorectalcancer.RecentstudieshaveidentifiedseveralmicroRNAsthataredysregulatedincolorectalcancerandthathavepotentialdiagnosticandprognosticvalue.
LongnoncodingRNAs(lncRNAs)areaclassofnoncodingRNAsthataremorethan200nucleotidesinlength.Althoughinitiallyconsidered"junk"DNA,recentstudieshaveshownthatlncRNAsplayacriticalroleintheregulationofgeneexpressionandcellularprocesses.DysregulationoflncRNAshasbeenimplicatedinthedevelopmentandprogressionofvariouscancers,includingcolorectalcancer.SeverallncRNAshavebeenidentifiedthataredysregulatedincolorectalcancerandthathavepotentialdiagnosticandtherapeuticvalue.
Tumor-associatedantigens(TAAs)areproteinsthatareexpressedbycancercellsandthatarerecognizedbytheimmunesystem.SeveralTAAshavebeenidentifiedthatareexpressedincolorectalcancerandthathavepotentialdiagnostic,prognostic,andtherapeuticvalue.Forexample,carcinoembryonicantigen(CEA)isaglycoproteinthatisoverexpressedinmanytypesofcancer,includingcolorectalcancer.CEAhasbeenusedasadiagnosticmarkerandasatargetforimmunotherapyincolorectalcancer.
Inconclusion,colorectalcancerisacomplexdiseasethatinvolvesthedysregulationofmultiplemolecularpathways.Abetterunderstandingofthemolecularmechanismsthatunderliethedevelopmentandprogressionofcolorectalcanceriscriticalforthedevelopmentofeffectivetherapies.Theidentificationofmolecularmarkers,suchasTwist,β-catenin,andE-cadherin,microRNAs,lncRNAs,andTAAs,hasprovidedvaluableinsightsintothemolecularmechanismsofcolorectalcancerandhasopenedupnewavenuesfordiagnosisandtreatment.FurtherresearchinthisareaisneededtodevelopmoreeffectivetherapiesforthisdevastatingdiseaseInthepastfewdecades,significantadvanceshavebeenmadeinourunderstandingofthemechanismsthatdrivethedevelopmentandprogressionofcolorectalcancer.Oneofthecriticalfactorsincolorectalcanceristheactivationofoncogenesandthelossoftumorsuppressors,whichdrivecellproliferation,differentiation,andapoptosis.Mutationsandalterationsinspecificgenes,includingAPC,K-ras,andTP53,arecommonlyobservedincolorectalcancer.
ThelossofE-cadherinandtheactivationofβ-cateninsignalingarealsoessentialeventsincolorectalcancerdevelopment.E-cadherinisacalcium-dependentcelladhesionproteinthatplaysacriticalroleincell-to-celladhesionandmaintainstheepithelialphenotype.Incontrast,β-cateninisacriticalmediatoroftheWntsignalingpathwayandplaysacriticalroleinregulatingcellproliferationanddifferentiation.Incolorectalcancer,lossofE-cadherinandactivationofβ-cateninsignalingdisrupttheepithelialbarrierandpromotetumorcellproliferationandinvasion.
Anothercriticalmechanismdrivingcolorectalcancerdevelopmentisepithelial-mesenchymaltransition(EMT).EMTisaprocessbywhichepithelialcellslosetheircell-celladhesionandacquiremesenchymalcharacteristics,allowingthemtomigrateandinvadesurroundingtissues.EMTisregulatedbytranscriptionfactorssuchasTwist,Snail,andSlug,whichplayacriticalroleintheprogressionofcolorectalcancer.
Recently,severalstudieshavealsoidentifiedtheroleofnon-codingRNAs(ncRNAs)inthedevelopmentandprogressionofcolorectalcancer.MicroRNAs(miRNAs)andlongnon-codingRNAs(lncRNAs)havebeenreportedtoregulategeneexpressionatthepost-transcriptionallevelandplayacriticalroleinregulatingcellularprocessessuchascellproliferation,apoptosis,angiogenesis,andinvasion.ThealteredexpressionofspecificmiRNAsandlncRNAshasbeenlinkedtothedevelopmentandprogressionofcolorectalcancer,makingthempotentialdiagnosticandtherapeutictargets.
Targetedtherapieshavealsobeendevelopedforcolorectalcancerbasedontheidentificationoftumor-associatedantigens(TAAs).TAAsareproteinsthatarepreferentiallyexpressedbytumorcellsandshowlimitedexpressioninnormaltissue,makingthemattractivetargetsforcancertherapy.AntibodiestargetingTAAssuchasCEAandEpCAMhavebeendevelopedandshownefficacyinclinicaltrials.
Inconclusion,colorectalcance
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