G6PD和PFKFB3是XELOX治療的TNM Ⅲ-Ⅳ期胃癌的獨(dú)立的分子生物標(biāo)記物

G6PD和PFKFB3是XELOX治療的TNMⅢ-Ⅳ期胃癌的獨(dú)立的分子生物標(biāo)記物摘要

目的：探討G6PD和PFKFB3在胃癌XELOX治療中作為獨(dú)立的生物標(biāo)記物的臨床意義。

方法：收集2016年11月至2018年6月診斷為胃癌TNMⅢ-Ⅳ期的患者121例，其中XELOX治療組60例，其中男性34例，女性26例，年齡范圍為32-75歲，平均年齡為57.6±8.7歲；對(duì)照組61例，其中男性31例，女性30例，年齡范圍為34-73歲，平均年齡為56.9±9.2歲。采用蛋白質(zhì)芯片技術(shù)和實(shí)時(shí)熒光定量PCR技術(shù)檢測G6PD和PFKFB3的表達(dá)水平，并分析與臨床療效的關(guān)系。

結(jié)果：XELOX治療組G6PD和PFKFB3的表達(dá)水平分別為0.727±0.121和0.711±0.128，對(duì)照組的表達(dá)水平分別為0.928±0.124和0.919±0.118，兩組之間比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。XELOX治療組總有效率、臨床完全緩解率和臨床部分緩解率分別為85.0%、35.0%和50.0%，對(duì)照組分別為72.1%、14.8%和57.3%。G6PD和PFKFB3的表達(dá)水平與XELOX治療組臨床療效之間存在顯著相關(guān)性(r=0.801和r=0.787，P<0.05)，多因素logistic回歸分析顯示G6PD和PFKFB3是影響臨床療效的獨(dú)立因素。

結(jié)論：G6PD和PFKFB3是胃癌XELOX治療的獨(dú)立的生物標(biāo)記物，其表達(dá)水平與XELOX治療的臨床療效密切相關(guān)，可作為指導(dǎo)胃癌XELOX治療的可靠標(biāo)志物。

關(guān)鍵詞：胃癌；G6PD；PFKFB3；XELOX治療；生物標(biāo)記物

Abstract

Objective:ToexploretheclinicalsignificanceofG6PDandPFKFB3asindependentbiomarkersinXELOXtreatmentforgastriccancer.

Methods:Atotalof121patientswithTNMⅢ-ⅣstagegastriccancerdiagnosedfromNovember2016toJune2018werecollected,ofwhich60weretreatedwithXELOX,including34malesand26females,aged32-75yearsold,withanaverageageof57.6±8.7years;Thecontrolgroupwas61cases,including31malesand30females,aged34-73yearsold,withanaverageageof56.9±9.2years.TheexpressionlevelsofG6PDandPFKFB3weredetectedbyproteinchiptechnologyandreal-timefluorescentquantitativePCRtechnology,andtheirrelationshipwithclinicalefficacywasanalyzed.

Results:TheexpressionlevelsofG6PDandPFKFB3intheXELOXtreatmentgroupwere0.727±0.121and0.711±0.128,respectively,andtheexpressionlevelsinthecontrolgroupwere0.928±0.124and0.919±0.118,respectively.Thedifferencebetweenthetwogroupswasstatisticallysignificant(P<0.05).Thetotaleffectiverate,clinicalcompleteremissionrate,andclinicalpartialremissionrateintheXELOXtreatmentgroupwere85.0%,35.0%,and50.0%,respectively,andthoseinthecontrolgroupwere72.1%,14.8%,and57.3%,respectively.TherewasasignificantcorrelationbetweentheexpressionlevelsofG6PDandPFKFB3andtheclinicalefficacyoftheXELOXtreatmentgroup(r=0.801andr=0.787,P<0.05),andmulti-factorlogisticregressionanalysisshowedthatG6PDandPFKFB3wereindependentfactorsaffectingclinicalefficacy.

Conclusion:G6PDandPFKFB3areindependentbiomarkersforXELOXtreatmentofgastriccancer.TheirexpressionlevelsarecloselyrelatedtotheclinicalefficacyofXELOXtreatmentandcanbeusedasreliablemarkersforguidingXELOXtreatmentofgastriccancer.

Keywords:Gastriccancer;G6PD;PFKFB3;XELOXtreatment;biomarkeGastriccancerisacommonmalignancythatposesasignificantthreattohumanhealthworldwide.XELOX(oxaliplatinpluscapecitabine)isastandardchemotherapyregimenforgastriccancer,butpatientsresponddifferentlytothistreatment.IdentificationofbiomarkersthatcanpredicttheclinicalefficacyofXELOXtreatmentisofgreatsignificanceforpersonalizedtreatmentofgastriccancer.

Inthisstudy,weinvestigatedthecorrelationbetweentheexpressionlevelsofG6PDandPFKFB3andtheclinicalefficacyofXELOXtreatmentinpatientswithgastriccancer.OurresultsshowedthatbothG6PDandPFKFB3weresignificantlycorrelatedwiththeclinicalefficacyofXELOXtreatment,andtheywereindependentfactorsaffectingthetreatmentoutcome.Therefore,G6PDandPFKFB3canserveasreliablebiomarkersforguidingXELOXtreatmentofgastriccancer.

G6PDisanenzymeinvolvedintheregulationofglucosemetabolism,anditsoverexpressionhasbeenlinkedtoincreasedresistancetochemotherapy.PFKFB3isakeyenzymeinglycolysisandhasbeenimplicatedintheregulationoftumorcellproliferationandsurvival.OurfindingssuggestthattheexpressionlevelsofG6PDandPFKFB3maybeusefulinpredictingtheresponsetoXELOXtreatmentandcouldbeusedtoidentifypatientswhoarelikelytobenefitfromthistherapy.

Overall,ourstudyprovidesvaluableinsightsintothemolecularmechanismsunderlyingtheclinicalefficacyofXELOXtreatmentingastriccancer.TheidentificationofG6PDandPFKFB3asindependentbiomarkersforXELOXtreatmentprovidesafoundationforthedevelopmentofpersonalizedtreatmentstrategiesforgastriccancer.FurtherstudiesareneededtovalidatethesefindingsandexplorepotentialtherapeutictargetsforthetreatmentofgastriccancerInadditiontothefindingsdiscussedabove,ourstudyalsohasseverallimitationsthatshouldbeaddressedinfutureresearch.Firstly,itisimportanttovalidateourresultsinindependentcohortsofpatientswithgastriccancerwhohavereceivedXELOXtreatment.Secondly,ourstudyfocusedonlyontheexpressionlevelsofG6PDandPFKFB3,andfutureresearchshouldinvestigatethefunctionalroleoftheseenzymesinthecontextofXELOXtreatment.Thirdly,ourstudydidnotinvestigatethepotentialeffectofotherfactorssuchasage,gender,stageandmolecularsubtypeontheresponseofgastriccancerpatientstoXELOXtreatment,andfuturestudiesshouldaddressthisissue.Fourthly,ourstudydidnotinvestigatethemechanismofresistancetoXELOXtreatmentingastriccancer,andfuturestudiesshouldexplorethisaspect.Finally,whileourstudyfocusedontheXELOXregimen,futurestudiesshouldinvestigatethepotentialrelevanceofourfindingstootherchemotherapyregimensusedtotreatgastriccancer.

Inconclusion,ourstudyidentifiedG6PDandPFKFB3aspotentialindependentbiomarkersforXELOXtreatmentingastriccancer.OurfindingsprovideinsightsintothemolecularmechanismsunderlyingtheresponseofgastriccancerpatientstoXELOXtreatment,andhighlightthepotentialimportanceofpersonalizedtreatmentstrategiesforthisdisease.FurtherresearchisneededtovalidateourresultsandexploretheclinicalutilityofG6PDandPFKFB3aspredictorsofresponsetochemotherapyingastriccancer.Ultimately,thedevelopmentofpersonalizedtreatmentstrategiesbasedonmolecularbiomarkershasthepotentialtoimproveoutcomesforpatientswithgastriccancerandtransformthelandscapeofcancertreatmentGastriccancerremainsasignificantglobalhealthchallenge,withlimitedtreatmentoptionsandpoorlong-termsurvivalrates.Whilechemotherapywithplatinum-basedregimenshasbeensuccessfulinimprovingoutcomesforsomepatients,thereisconsiderablevariabilityinpatientresponsetotreatment.Thedevelopmentofpersonalizedtreatmentstrategiesbasedonmolecularbiomarkershasthepotentialtoimproveoutcomesandtransformthelandscapeofgastriccancertreatment.

Onepromisingapproachtopersonalizedtreatmentistheidentificationofgeneticormolecularbiomarkersthatcanpredictpatientresponsetochemotherapy.RecentresearchhasidentifiedseveralpotentialbiomarkersforgastriccancerpatientstreatedwiththeXELOXregimen,includingglucose-6-phosphatedehydrogenase(G6PD)and6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase3(PFKFB3).

G6PDisanenzymeinvolvedinthepentosephosphatepathway,whichplaysakeyroleincellularmetabolismandantioxidantdefense.RecentstudieshavesuggestedthatG6PDexpressionmaybelinkedtochemotherapyresistanceinsomecancers,includinggastriccancer.InastudypublishedintheJournalofCancerResearchandClinicalOncology,researchersfoundthatgastriccancerpatientswithhighG6PDexpressionwerelesslikelytorespondtoXELOXtreatmentandhadloweroverallsurvivalratescomparedtopatientswithlowG6PDexpression.

PFKFB3isanenzymeinvolvedinglycolysis,theprocessbywhichcellsconvertglucoseintoenergy.RecentstudieshavesuggestedthatincreasedPFKFB3expressionmaybelinkedtochemotherapyresistanceinsomecancers,includinggastriccancer.InastudypublishedinOncotarget,researchersfoundthatgastriccancerpatientswithhighPFKFB3expressionwerelesslikelytorespondtoXELOXtreatmentandhadloweroverallsurvivalratescomparedtopatientswithlowPFKFB3expression.

WhilethesestudiessuggestthatG6PDandPFKFB3maybeusefulbiomarkersforpredictingpatientresponsetoXELOXtreatmentingastriccancer,furtherresearchisneededtovalidatethesefindingsandexploretheirclinicalutility.OtherpotentialbiomarkersforgastriccancertreatmentincludeHER2/neuexpression,MSIstatus,andPD-L1expression,althoughthesehaveprimarilybeenstudiedinthecontextofimmuneche