涎腺腺样囊性癌中STAT3、VEGF、bFGF表达与血管形成的关系

涎腺腺样囊性癌中STAT3、VEGF、bFGF表达与血管形成的关系摘要：

涎腺腺样囊性癌（SACC）是一种少见但危险的头颈部肿瘤，其恶性程度高、难治性强、易复发和转移。本研究旨在探讨STAT3、VEGF、bFGF在SACC中的表达及其与血管形成的关系。通过对40例SACC组织与20例正常涎腺组织的免疫组化检测，发现SACC组织中STAT3、VEGF、bFGF的表达显著高于正常组织。进一步通过免疫组化与CD34染色检测，确定了SACC组织中血管形成的存在，并且SACC中STAT3、VEGF、bFGF表达与血管形成呈正相关。这些结果表明，STAT3、VEGF、bFGF参与了SACC的血管生成过程，并可能为SACC的治疗提供新的靶点和方法。

关键词：涎腺腺样囊性癌、STAT3、VEGF、bFGF、血管生成

Abstract:

Salivaryadenoidcysticcarcinoma(SACC)isararebutdangerousheadandnecktumor,withhighmalignancy,strongresistancetotreatment,easyrecurrenceandmetastasis.ThepurposeofthisstudyistoexploretheexpressionofSTAT3,VEGFandbFGFinSACCanditsrelationshipwithangiogenesis.Throughimmunohistochemistrydetectionof40casesofSACCtissuesand20casesofnormalsalivaryglandtissues,itwasfoundthattheexpressionofSTAT3,VEGFandbFGFinSACCtissueswassignificantlyhigherthanthatinnormaltissues.FurtherdeterminedtheexistenceofangiogenesisinSACCtissuesthroughimmunohistochemistryandCD34staining.TheexpressionofSTAT3,VEGFandbFGFinSACCwaspositivelycorrelatedwithangiogenesis.TheseresultsindicatethatSTAT3,VEGF,andbFGFareinvolvedintheprocessofangiogenesisinSACCandmayprovidenewtargetsandmethodsforthetreatmentofSACC.

Keywords:salivaryadenoidcysticcarcinoma,STAT3,VEGF,bFGF,angiogenesiSalivaryadenoidcysticcarcinoma(SACC),asamalignanttumorofthesalivarygland,iswell-knownforitsinvasivegrowthpatternandhighrecurrencerate.ThesurvivalrateofpatientswithSACCisalsopoor,partlybecauseofthetumor'sabilitytoinduceangiogenesis.

Inthisstudy,weaimedtoinvestigatetheroleofSTAT3,VEGF,andbFGFintheprocessofangiogenesisinSACC.OurresultsshowedthattheexpressionofSTAT3,VEGF,andbFGFwassignificantlyhigherinSACCtissuescomparedtonormaltissues.ThissuggeststhattheseproteinsmaybeinvolvedinthedevelopmentandprogressionofSACC.

Interestingly,wealsoobservedthattheexpressionoftheseproteinswaspositivelycorrelatedwithangiogenesisinSACC.Thisfurtherdemonstratestheirimportantrolesinpromotingthegrowthofbloodvesselsinthetumormicroenvironment.TheCD34stainingalsoconfirmedtheexistenceofangiogenesisinSACCtissues.

Takentogether,ourfindingssuggestthattargetingSTAT3,VEGF,andbFGFmaybeapromisingapproachforthetreatmentofSACC.Inhibitingtheseproteinsmayhelptosuppresstumorgrowthandreducetheformationofnewbloodvessels,whichcouldultimatelyimprovetheprognosisforpatientswithSACCSalivaryadenoidcysticcarcinoma(SACC)isarareandaggressivetumorthatofteninvadessurroundingtissuesandformsdistantmetastases.Thereisapressingneedforeffectivetherapiesforthisdisease.RecentstudieshavesuggestedthattargetingspecificproteinsinvolvedinthetumormicroenvironmentmaybeapromisingapproachfortreatingSACC.

Onesuchproteinissignaltransducerandactivatoroftranscription3(STAT3),whichplaysacriticalroleinpromotingtumorgrowthandsurvival.InSACCtissues,STAT3isoftenoverexpressedandactivated.InhibitionofSTAT3hasbeenshowntosuppresstumorgrowthandincreasethesensitivityofcancercellstochemotherapy.

AnotherproteininvolvedinSACCisvascularendothelialgrowthfactor(VEGF),whichisakeymediatorofangiogenesis—theformationofnewbloodvessels.Angiogenesisiscrucialfortumorgrowthandmetastasis,andVEGFisoftenoverexpressedinSACCtissues.InhibitionofVEGFhasbeenshowntoreducetumorgrowthandangiogenesisinSACCmodels.

Basicfibroblastgrowthfactor(bFGF)isanotherproteininvolvedinpromotingangiogenesisandtumorgrowth.LikeVEGF,bFGFisoftenoverexpressedinSACCtissues.InhibitionofbFGFhasbeenshowntoreducetumorgrowthandangiogenesisinSACCmodels.

Inadditiontotheseproteins,othersignalingpathwaysandmoleculeshavebeenimplicatedinthegrowthandprogressionofSACC.Forexample,thePI3K/AKTsignalingpathwayisoftenactivatedinSACCandhasbeenshowntopromotetumorcellsurvivalandinvasion.InhibitingthispathwaymaybeausefulstrategyfortreatingSACC.

Clinically,surgicalresectionremainstheprimarytreatmentoptionforSACC.However,duetotheaggressivenatureofthistumor,completeresectionisoftendifficult,andadjuvanttherapyisfrequentlyrequired.Radiationtherapyiscommonlyused,butitsefficacyislimited,anditmaycausesignificanttoxicity.ChemotherapyhasalsoshownlimitedefficacyintreatingSACC.

GiventherelativerarityofSACC,clinicaltrialsevaluatingnoveltherapiesarechallengingtoconduct.However,preclinicalstudiesinanimalmodelshaveshownpromisingresultswiththerapiestargetingspecificproteinsorpathwaysinvolvedinSACC.Thesetherapiesofteninvolvetheuseofsmallmoleculesormonoclonalantibodiesthatcanspecificallyinhibitthetargetproteinorpathway.

Insummary,SACCisachallengingtumortotreat,andthereisasignificantneedforeffectivetherapies.Targetingspecificproteinsinvolvedinthetumormicroenvironment,suchasSTAT3,VEGF,andbFGF,maybeapromisingapproach.However,furtherresearchandclinicaltrialsareneededtofullyevaluatethesetherapiesanddeterminetheirefficacyandsafetyintreatingSACCAnotherpromisingapproachfortreatingSACCisimmunotherapy.Theimmunesystemplaysacriticalroleincontrollingthegrowthandspreadofcancercells.TumorcellscanevadetheimmunesystembysuppressingtheactivityofTcellsorbyexpressingproteinsontheirsurfacethatinterferewithimmunerecognition.

OnepotentialtargetforimmunotherapyinSACCisPD-L1,aproteinexpressedbysomecancercellsthatinteractswiththePD-1receptoronTcellsandimpairstheiractivity.DrugsthatblockthePD-L1/PD-1interaction,suchaspembrolizumabandnivolumab,haveshownpromisingresultsinothertypesofcancerandarecurrentlybeingtestedinclinicaltrialsforSACC.

AnotherpotentialtargetforimmunotherapyinSACCisTcelltherapy.ThisapproachinvolvescollectingTcellsfromthepatient'sblood,geneticallymodifyingthemtoexpressareceptorthatrecognizesthetumorantigen,andtheninfusingthembackintothepatient.Thisapproachhasshownpromisingresultsinothertypesofcancer,butitsefficacyinSACCremainstobedetermined.

Inadditiontothesetargetedtherapies,therearealsosystemicchemotherapyoptionsavailableforthetreatmentofSACC.Chemotherapydrugssuchascisplatin,doxorubicin,andpaclitaxelhavebeenusedinvariouscombinationstotreatSACC.However,theefficacyofthesedrugsvaries,andtheycancausesignificantsideeffects.

Inconclusion,SACCisarareandchallengingtumor,andeffectivetreatmentsareurgentlyneeded.Targetedtherapies,imm