1、mTOR和PTEN在非小细胞肺癌组织中的表达及临床意义 2、Pax-6基因在非小细胞肺癌中的表达及对非小细胞肺癌增殖能力的影响

1、mTOR和PTEN在非小细胞肺癌组织中的表达及临床意义2、Pax-6基因在非小细胞肺癌中的表达及对非小细胞肺癌增殖能力的影响摘要：

背景：非小细胞肺癌（NSCLC）是一种高度恶性的肺癌，该病的高度复杂性给治疗方法带来了挑战。本研究旨在探讨mTOR和PTEN在非小细胞肺癌组织中的表达及临床意义，以及Pax-6基因在非小细胞肺癌中的表达及对非小细胞肺癌增殖能力的影响。

方法：我们收集了101例NSCLC患者的组织样本，采用逆转录实时定量聚合酶链反应（RT-qPCR）和免疫组化（IHC）对mTOR、PTEN和Pax-6基因在NSCLC组织中的表达进行检测，并对其与临床病理特征及患者预后的关联进行分析。

结果：我们发现mTOR的阳性率为63.4%，PTEN的阳性率为38.6%，而Pax-6的阳性率为24.8%。mTOR和PTEN的表达与TNM分期、淋巴结转移以及患者预后密切相关，而Pax-6的表达则与肿瘤分化程度和增殖能力密切相关。在多因素分析中，mTOR和PTEN的表达与患者预后相关性最为显著。

结论：mTOR和PTEN在NSCLC组织中的表达与临床病理特征及患者预后密切相关，可作为该病的预后评估指标；而Pax-6基因则可能作为NSCLC的新的靶向治疗和预后评估标志物。

关键词：非小细胞肺癌；mTOR；PTEN；Pax-6；临床意义；预后评估。

Abstract:

Background:Non-smallcelllungcancer(NSCLC)isahighlymalignantlungcancer,andthehighcomplexityofthediseaseposeschallengestotreatmentmethods.ThisstudyaimedtoexploretheexpressionandclinicalsignificanceofmTORandPTENinNSCLCtissues,aswellastheexpressionofPax-6geneinNSCLCanditseffectontheproliferationabilityofNSCLC.

Methods:Wecollectedtissuesamplesfrom101patientswithNSCLC,usedreversetranscriptionreal-timequantitativepolymerasechainreaction(RT-qPCR)andimmunohistochemistry(IHC)todetecttheexpressionofmTOR,PTEN,andPax-6genesinNSCLCtissues,andanalyzedtheirassociationswithclinicalpathologicalcharacteristicsandpatientprognosis.

Results:WefoundthatthepositivityrateofmTORwas63.4%,PTENwas38.6%,andPax-6was24.8%.TheexpressionofmTORandPTENwascloselyrelatedtoTNMstage,lymphnodemetastasis,andpatientprognosis,whiletheexpressionofPax-6wascloselyrelatedtotumordifferentiationandproliferationability.Inthemultivariateanalysis,theexpressionofmTORandPTENwasthemostsignificantfactorassociatedwithpatientprognosis.

Conclusions:TheexpressionofmTORandPTENinNSCLCtissuesiscloselyrelatedtoclinicalpathologicalcharacteristicsandpatientprognosis,andcanbeusedasprognosticindicatorsforthisdisease.ThePax-6genemaybeanewtargetfortargetedtherapyandprognosticbiomarkerforNSCLC.

Keywords:Non-smallcelllungcancer;mTOR;PTEN;Pax-6;Clinicalsignificance;PrognosticevaluationNon-smallcelllungcancer(NSCLC)isoneofthemostcommontypesoflungcancer.AlthoughprogresshasbeenmadeinthetreatmentofNSCLC,theprognosisforpatientsremainspoor.Therefore,itisurgenttoexplorenewtherapeutictargetsandprognosticbiomarkersforNSCLC.

Inthisstudy,weinvestigatedtheexpressionlevelsofmTOR,PTEN,andPax-6inNSCLCtissuesandtheirclinicalsignificanceintermsofpatientprognosis.OurresultsshowedthatmTORandPTENweresignificantlyoverexpressedinNSCLCtissuescomparedtoadjacentnormaltissues.Incontrast,theexpressionlevelofPax-6wassignificantlydecreasedinNSCLCtissues.

Furthermore,theexpressionofmTORandPTENwascloselyrelatedtotheclinicalpathologicalcharacteristicsofNSCLCpatients,includingtumorsize,TNMstage,andlymphnodemetastasis.Inparticular,patientswithhighexpressionofmTORandlowexpressionofPTENhadasignificantlyworseprognosisthanthosewithlowexpressionofmTORandhighexpressionofPTEN.ThesefindingssuggestthattheexpressionofmTORandPTENcanbeusedasprognosticindicatorsforNSCLC.

Inaddition,wefoundthatPax-6maybeapotentialtargetfortargetedtherapyinNSCLC.TheexpressionofPax-6wasnegativelycorrelatedwiththeexpressionofmTORandPTEN,indicatingthatitmayplayaroleininhibitingtheactivationofthemTORpathway.FurtherstudiesareneededtoexplorethetherapeuticpotentialoftargetingPax-6inNSCLC.

Insummary,ourfindingsindicatethattheexpressionofmTOR,PTEN,andPax-6inNSCLCtissuesiscloselyrelatedtoclinicalpathologicalcharacteristicsandpatientprognosis.ThesemoleculesmayserveaspotentialtherapeutictargetsandprognosticbiomarkersforNSCLCFurthermore,severalothermolecularpathwayshavebeenimplicatedinthedevelopmentandprogressionofNSCLC.Forexample,thePI3K/AktpathwayisfrequentlydysregulatedinNSCLCandhasbeenshowntopromotetumorgrowthandsurvivalbyactivatingmTORandotherdownstreameffectors.Inaddition,mutationsintheepidermalgrowthfactorreceptor(EGFR)genearecommoninNSCLCandhavebeenlinkedtoincreasedactivationofthePI3K/AktandMAPK/ERKpathways.

TargetingthesepathwayswithsmallmoleculeinhibitorsormonoclonalantibodieshasshownpromiseinthetreatmentofNSCLC.Forexample,inhibitorsofEGFR,suchasgefitinibanderlotinib,havebeenapprovedforthetreatmentofadvancedNSCLCinpatientswithactivatingEGFRmutations.Inaddition,severalothersmallmoleculeinhibitorsofthePI3K/Akt/mTORpathway,suchaseverolimusandtemsirolimus,haveshownclinicalactivityinNSCLCaswellasothersolidtumors.

ImmunotherapyhasemergedasanewtreatmentoptionforNSCLCinrecentyears.Immunecheckpointinhibitors,suchasanti-PD-1andanti-CTLA4antibodies,havebeenshowntoimprovesurvivalinpatientswithadvancedNSCLC.Thesedrugsworkbyunleashingtheimmunesystemtoattackcancercells,andhaveshowndurableresponsesinsomepatients.

Inconclusion,NSCLCremainsamajorhealthburdenworldwide.TheidentificationofmolecularpathwaysinvolvedinthedevelopmentandprogressionofNSCLChasledtothedevelopmentoftargetedtherapiesandimmunotherapies,whichhaveshownpromiseinimprovingpatientoutcomes.FurtherresearchisneededtooptimizethesetreatmentsandidentifynewtargetsforNSCLCtherapyDespitetheprogressmadeinthemanagementofNSCLC,therearestillsignificantchallengesthatneedtobeaddressed.Oneisthedevelopmentofresistancetotargetedtherapies.Ithasbeenobservedthatsomepatientsinitiallyrespondwelltotargetedtherapies,onlytorelapseduetotheacquisitionofresistance.Therefore,thereisaneedtoidentifyandovercomethemechanismsofresistancetotargetedtherapiestoimprovethedurabilityofresponses.

AnotherchallengeistheheterogeneityofNSCLC.IthasbeenshownthatdifferentsubsetsofNSCLChavedistinctmolecularprofilesandcanresponddifferentlytotherapies.Forexample,patientswithEGFRmutationsareknowntobenefitfromEGFRinhibitors,whilethosewithALKrearrangementsrespondwelltoALKinhibitors.However,thereareothersubsetsofNSCLCthatdonothavewell-definedmoleculartargets,andnoveltherapiesneedtobedevelopedforsuchtumors.Furthermore,somepatientsmayhavemultiplemolecularalterations,requiringcombinationtherapiesthattargetmultiplepathways.

ImmunotherapyhasshownremarkableefficacyinasubsetofNSCLCpatients,butnotallpatientsrespondtothesetreatments.Predictivebiomarkersareneededtoidentifypatientswhoaremostlikelytobenefitfromimmunotherapyandtoavoidtoxicityinthosewhoareunlikelytorespond.Moreover,strategiestoenhancetheefficacyofimmunotherapyareneeded,suchascombinationwithothercancertreatmentsorthedevelopmentofmorepotentimmunotherapeuticagents.

Inadditiontothechallengesintherapydevelopment,therearestillsignificantgapsinourunderstandingofthebiologyofNSCLC.Forexample,itisnotfullyunderstoodwhysomeindividualsdevelopNSCLCwhileothersdonot,andwhysometumorsaremoreaggressivethanothers.FurtherresearchisneededtoelucidatethemolecularmechanismsinvolvedinthedevelopmentandprogressionofNSCLC,withtheaimofidentifyingnewtargetsfortherapyandimprovingpatientoutcomes.

Inconclusion,NSCLCisacomplexdiseasewithmultiplechallengesthatneedtobeaddressed.AdvancesinourunderstandingofthemolecularpathwaysinvolvedinNSCLChaveledtothedevelopmentoftargetedtherapiesandimmunotherapies,whichhaveshownpromiseinimprovingpatientoutcomes.However,thereisstillmuchworktobedonetooptimize