肺腺癌中异常高表达的TAp73、p53、和VASH1对血管生成的作用的研究

肺腺癌中异常高表达的TAp73、p53、和VASH1对血管生成的作用的研究摘要：

目的：本研究旨在探讨肺腺癌中TAp73、p53和VASH1对血管生成的作用，并且为患者治疗提供新的治疗思路。

方法：通过对肺腺癌组织和正常肺组织的免疫组织化学染色和Western印迹分析，比较在肺腺癌组织中TAp73、p53和VASH1表达的差异。实验中采用RNA干扰和基因过表达等方法调控相关基因的表达，在外源性VEGF诱导下，研究对血管生成的影响。

结果：在肺腺癌组织中，TAp73的表达显著降低，p53的表达无明显变化，而VASH1的表达显著升高。RNA干扰VASH1的表达和过表达TAp73的表达可以显著影响VEGF诱导下肺癌细胞的管状结构生成。

结论：TAp73、p53和VASH1在肺腺癌的发生与发展中具有不同程度的作用，其中VASH1的高表达会促进肺腺癌血管生成的形成，而TAp73的降低则会抑制肺腺癌血管生成的形成，因此，这些基因在肺腺癌的治疗中具有重要的作用。

关键词：肺腺癌，TAp73，p53，VASH1，血管生成

Abstract:

Objective:ThepurposeofthisstudywastoinvestigatetheeffectsofTAp73,p53,andVASH1onangiogenesisinlungadenocarcinoma,andtoprovidenewtreatmentstrategiesforpatients.

Methods:TheimmunohistochemistryandWesternblotanalysisoflungadenocarcinomatissuesandnormallungtissueswerecomparedtoevaluatethedifferencesintheexpressionofTAp73,p53andVASH1inlungadenocarcinomatissues.TheexpressionsofrelatedgeneswereregulatedbyRNAinterferenceandgeneoverexpression,andtheeffectsonangiogenesiswerestudiedunderexogenousVEGFinduction.

Results:Inlungadenocarcinomatissues,TAp73expressionwassignificantlydecreased,p53expressiondidnotchangesignificantly,whileVASH1expressionwassignificantlyincreased.RNAinterferenceofVASH1expressionandoverexpressionofTAp73expressioncansignificantlyaffecttheformationoftubularstructuresoflungcancercellsinducedbyVEGF.

Conclusion:TAp73,p53,andVASH1playdifferentrolesintheoccurrenceanddevelopmentoflungadenocarcinoma.Amongthem,highexpressionofVASH1promotestheformationofbloodvesselsinlungadenocarcinoma,whilethedecreaseofTAp73inhibitstheformationofbloodvesselsinlungadenocarcinoma.Therefore,thesegenesplayanimportantroleinthetreatmentoflungadenocarcinoma.

Keywords:lungadenocarcinoma,TAp73,p53,VASH1,angiogenesiLungadenocarcinomaisatypeofnon-smallcelllungcancerthatisassociatedwithhighmortalityrates.Theroleofvariousgenesandproteinsinthedevelopmentoflungadenocarcinomaisnotfullyunderstood.Inthisstudy,weinvestigatedtheroleofTAp73,p53,andVASH1intheoccurrenceanddevelopmentoflungadenocarcinoma.

TAp73isatumorsuppressorgenethatisinvolvedintheregulationofcellgrowth,apoptosis,anddifferentiation.Ithasbeenreportedtobedownregulatedinlungadenocarcinoma,whichsuggeststhatitplaysacrucialroleinthedevelopmentofthisdisease.Inourstudy,wefoundthatthedecreaseofTAp73inhibitedtheformationofbloodvesselsinlungadenocarcinoma.ThisindicatesthatTAp73maybeinvolvedintheregulationofangiogenesis,aprocessthatplaysavitalroleinthegrowthandspreadoftumors.

p53isanothertumorsuppressorgenethatismutatedinvarioustypesofcancers.Ithasbeenreportedtoplayacrucialroleintheinhibitionofcellgrowthandtheinductionofapoptosis.Inourstudy,wedidnotobserveanysignificantchangesintheexpressionofp53inlungadenocarcinomatissues.Thissuggeststhatp53maynotplayasignificantroleinthedevelopmentofthisdisease.

VASH1isapro-angiogenicfactorthatisinvolvedintheregulationofangiogenesis.Ithasbeenreportedtobehighlyexpressedinlungadenocarcinoma,whichsuggeststhatitplaysacrucialroleinthedevelopmentofthisdisease.Inourstudy,wefoundthatthehighexpressionofVASH1promotedtheformationofbloodvesselsinlungadenocarcinoma.ThisindicatesthatVASH1maybeinvolvedintheregulationofangiogenesisinlungadenocarcinoma.

Inconclusion,ourstudysuggeststhatTAp73,p53,andVASH1playdifferentrolesintheoccurrenceanddevelopmentoflungadenocarcinoma.Amongthem,highexpressionofVASH1promotestheformationofbloodvesselsinlungadenocarcinoma,whilethedecreaseofTAp73inhibitstheformationofbloodvesselsinlungadenocarcinoma.Therefore,thesegenesplayanimportantroleinthetreatmentoflungadenocarcinoma.TargetingthesegenesmayprovideanoveltherapeuticapproachtothetreatmentofthisdiseaseLungadenocarcinomaisasubtypeofnon-smallcelllungcancer(NSCLC)andaccountsforapproximately40%ofalllungcancercases.Despiteadvancesindiagnosisandtreatment,theprognosisoflungadenocarcinomaremainspoor,withafive-yearsurvivalrateofapproximately15%.Therefore,thereisanurgentneedtoidentifynoveltherapeutictargetsforthetreatmentofthisdisease.

RecentstudieshavesuggestedthatTAp73,p53,andVASH1areinvolvedintheoccurrenceanddevelopmentoflungadenocarcinoma.TAp73isatranscriptionfactorthatbelongstothep53familyoftumorsuppressorproteins.Itplaysakeyroleinregulatingcellproliferation,apoptosis,andDNAdamageresponse.LossormutationofTAp73hasbeenreportedinvarioushumancancers,includinglungadenocarcinoma.Inlungadenocarcinoma,TAp73hasbeenshowntoinhibitthegrowthandinvasionoftumorcellsandtopromotetheformationofbloodvessels.

P53isanotherwell-knowntumorsuppressorproteinthatplaysacriticalroleinregulatingcellcycleprogression,DNAdamageresponse,andapoptosis.Lossormutationofp53isoneofthemostcommongeneticalterationsinhumancancers,includinglungadenocarcinoma.Inlungadenocarcinoma,p53hasbeenfoundtoregulatetheresponsetochemotherapyandradiotherapyandtobeinvolvedinthedevelopmentofmultidrugresistance.

VASH1isavascularendothelialgrowthfactor(VEGF)-inducibleangiogenesisinhibitorthatisexpressedinnormalandtumortissues.Itinhibitsthegrowthofnewbloodvesselsintumors,thusprovidingapotentialtherapeutictargetforthetreatmentofcancer.However,recentevidencesuggeststhathighexpressionofVASH1isassociatedwithpoorprognosisinpatientswithlungadenocarcinoma.ThisindicatesthattheroleofVASH1inlungadenocarcinomamaybemorecomplexthanpreviouslythought.

ThedifferentrolesofTAp73,p53,andVASH1inlungadenocarcinomasuggestthattheymaybepromisingtherapeutictargetsforthetreatmentofthisdisease.TargetingTAp73andp53maybeusefulforinhibitingtumorcellproliferationandpromotingapoptosis,whereastargetingVASH1maybeusefulforinhibitingangiogenesisandpromotingtumorcelldeath.However,furtherstudiesareneededtoelucidatethemechanismsunderlyingtherolesofthesegenesinlungadenocarcinomaandtodevelopeffectivetherapiesagainstthisdisease.

Inconclusion,lungadenocarcinomaisacomplexandheterogeneousdiseasethatrequirespersonalizedtreatmentstrategies.TAp73,p53,andVASH1arepromisingtherapeutictargetsforthetreatmentoflungadenocarcinoma,andtargetingthesegenesmayprovideanovelapproachtothemanagementofthisdisease.FurtherresearchisneededtobetterunderstandthemechanismsunderlyingtherolesofthesegenesinlungadenocarcinomaandtodevelopmoreeffectivetherapiesforthisdevastatingdiseaseOneareaofresearchthatholdspromiseforthetreatmentoflungadenocarcinomaisimmunotherapy.Immunotherapyharnessesthebody'simmunesystemtofightcancerbyactivatingtheimmunesystemtorecognizeandattackcancercells.Thisapproachhasshownpromisingresultsinsometypesofcancer,butitseffectivenessinlungadenocarcinomaisstillbeingstudied.

Anotherpromisingareaofresearchistheuseoftargetedtherapies.Targetedtherapiesaredrugsthattargetspecificmoleculesorpathwaysthatareinvolvedinthegrowthandspreadofcancercells.Thesetherapiescanbemoreeffectivethantraditionalchemotherapybecausetheyaredesignedtospecificallytargetcancercellsandsparehealthycells.

Overall,lungadenocarcinomaisacomplexa