电压门控质子通道蛋白hv1在结肠癌中的表达和临床意义-翟立广-陈国荣

Hv1：2014-12-26；：2015-03-15：（201203076）：，E-mail：[e-mail]1，2（1．，463000；2．，453000）：［］Hv1。［］200452008587；8730Hv1。Cox。［］Hv1，。Hv1、、T、、（P0.05）。Kaplan-Meier，Hv1，Hv1，Hv1（46vs.53，P0.05），（36vs.49，P0.05）。COXHv1（P=0.014）（P=0.037）。［］Hv1，，。：Hv1；；；：R735.3：A：1004-0242（2016）02-0150-05doi：10.11735/j.issn.1004-0242.2016.02.A014ExpressionandClinicopathologicalSignificanceofVolt-age-gatedProtonChannelHv1inColonCancerTissuesZHAILi-guang1,CHENGuo-rong2（1.People’sLiberationArmy(PLA)159thHospital，Zhumadian463000，China；2.TheThirdAffiliatedHospitalofXinxiangMedicalUniversity,Xinxiang453000，China）Abstract：［Purpose］Toinvestigatetheexpressionandclinicopathologicalsignificanceofvoltage-gatedprotonchannelHv1incoloncancertissues.［Methods］Clinicopathologicaldataof87pa-tientswithcoloncancerhospitalizedfromMay,2004toMay,2008wereretrospectivelyreviewed.Expressionofvoltage-gatedprotonchannelHv1in87caseswithcoloncancertissuesand30caseswithadjacentnormaltissueswasdeterminedbyimmnunohistochemistry(IHC).Coxproportionalhazardregressionmodelanalysiswasperformedtoanalyzetheindependentprognosticfactorsofpatientswithcoloncancer.TheinfluenceofHv1expressionontheoverallsurvivalandrecurrence-freesurvivalofpatientswithcoloncancerwasanalyzedbyKaplan-MeiermethodwithLog-ranktest.［Results］Hv1proteinwaspositivelyexpressedincoloncancertissues,whilenegativelyex-pressedinadjacentnormaltissues.Hv1expressionincoloncancertissuessignificantlycorrelatedwithpatients’age,tumorsize,Tstage,lymphnodestatus,distantmetastasisandclinicalstage.CoxproportionalhazardregressionanalysisindicatedthatHv1expressionwasindependentprog-nosticfactorofoverallsurvival(P=0.014)andrecurrence-freesurvival(P=0.037).Kaplan-Meiersur-vivalanalysisshowedthatpatientswithhighHv1expreesionhadpoorerprognosisthanthosewithlowHv1expression.ComparedwithpatientswithlowHv1expression,patientswithhighHv1ex-pressionhadashortermediansurvival(46monthsvs53months,P0.05)andshorterrecurrence-freesurvival(36monthsvs49months，P0.05).［Conclusion］Voltage-gatedprotonchannelproteinHv1,positivelyexpressedincoloncancertissues,isindependentprognosticfactorofpatientswithcoloncancer.Hv1isapromisingpotentialtargetfordevelopingnewmethodsoftumortherapy.Keywords：voltage-gatedprotonchannelHv1；coloncancer；recurrence；prognosisHv1（H+），［1，2］，，［3］。，Hv1MB-231150，siRNAHv1MB-231［4］；，Hv1、、、［3］。Hv1，Hv1。11.1200452008587。8761.3，43，44。25，26，36。＜5cm34，≥5cm53。42。Hv1。，20132，9。1.28730，4μm，，70℃48h。、、，50μlHv1（）4℃，37℃30min，DAB，。，，，。。。10（×400），100。，，1~4，≤25%，26%~50%，51%~75%，76%~100%。0~3，、、。，4，≤4。1.3SPSS19.0。Kaplan-Meier，Log-rank；COX。P0.05。22.1Hv1Hv1（Figure1A，1B），30（Figure1C）。Hv1、、T、、（P0.05）（Table1）。2.2Hv1Hv1，Hv1（46vs.53，P0.05）（Figure2A），（36A：Highexpression；B：Lowexpression；C：LowexpressioninadjacentnormaltissuesABC151χ≥≥vs.49，P0.05）（Figure2B）。（recurrence-freesurvival，RFS）Hv1、、T、、（P0.05）（Table2）。（overallsurvival，OS）Hv1、、T、、(P0.05）（Table3）。3［5］。CEACA199，，。Hv1，Hv1,，Hv1，，Hv1、、T、、。Kaplan-Meier，Hv1，Hv1（46vs.53，P0.05）；COXHv1；，Hv1，Hv1Table1RelationshipbetweenHv1expressionincoloncancertissuesandclinicopathologicalparametersABFigure2TheOSandRFSsurvivalcurvein87caseswithcoloncancerHvlexpressionLowHighLow-censoredHigh-censoredHvlexpressionLowHighLow-censoredHigh-censoredP0.05P0.0501020304050601.00.80.60.40.2Overallsurvival1.00.80.60.40.2Recurrence-freesurvival(RFS)0102030405060Time(months)Time(months)1522016252Table3Coxproportionalhazardsanalysisoftheindependentpredictivefactorsofoverallsurvival（36vs.49，P0.05）。COXHv1。Hv1H+，，。，。，，H+，Na+/H+，HCO3/，；、［6~9］。［10~14］。RNA［10,15］；H+，、、pH，，Caspase，［16~19］；，。Hv1，，Hv1，。，Hv1。：[1]MeitzlerJL，AntonyS，WuY，etal.NADPHoxidases：aperspectiveonreac-tiveoxygenspeciesproductionintumorbiology[J].AntioxidRedoxSignal，2014，20(17)：2873-2889.[2]DeCourseyTE，HoslerJ.Philosophyofvoltage-gatedprotonchannels[J].JRSocInterface，2014，11(92)：20130799.[3]WangY，LiSJ，WuX，etal.Clinicopatho-logicalandbiologicalsignificanceofhu-manvoltage-gatedprotonchannelHv1proteinoverexpressioninbreastcancer[J].JBiolChem，2012，287(17)：13877-13888.[4]WangY，LiSJ，PanJ，etal.Specificexpressionofthehu-manvoltage-gatedprotonchannelHv1inhighlymetastat-icbreastcancercells，promotestumorprogressionandmetastasis[J].BiochemBiophysResCommun，2011，412(2)：353-359.[5]TorreLA，BrayF，SiegelRL，etal.Globalcancerstatis-tics，2012[J].CACancerJClin，2015，65(2)：87-108.[6]SpugniniEP，SonveauxP，StockC，etal.Protonchannelsandexchangersincancer[J].BiochimBiophysActa，2014，Pii：S0005-2736(14)00350-2.[Epubaheadofprint][7]LutzNW，LeFurY，ChicheJ，etal.QuantitativeinvivocharacterizationofintracellularandextracellularpHpro-filesinheterogeneoustumors：anovelmethodenablingmultiparametricpHanalysis[J].CancerRes，2013，73(15)：4616-4628.[8]NdoloRA，LuanY，DuanS，etal.Lysosomotropicproper-tiesofweaklybasicanticanceragentspromotecancercellselectivityinvitro[J].PLoSOne，2012，7(11)：e49366.[9]SwietachP，HulikovaA，PatiarS，etal.Importanceofin-tracellularpHindeterminingtheuptakeandefficacyoftheweaklybasicchemoth