决策树是通过递回分割和企业分配决策

AFive-GeneSignatureandClinicalOutcome

inNon–Small-CellLungCancer

From:nengljmed356;1january4,2023By:Hsuan-YuChen,M.Sc.,Sung-LiangYu,Ph.D.,etalReporter:R6謝廣宇

Background

Currentstagingmethodsareinadequateforpredictingoutcomedevelopeda5-genesignaturenon–small-celllungcancer(NSCLC)—mostcommoncauseofdeathfromcancerworldwiderelapseratewithearly-stageNSCLCis40%within5yearsafterpotentiallycurativetreatment決策樹是通過遞迴分割（recursivepartitioning）建立而成，遞迴分割是一種把資料分割成不同小的部分的疊代過程cDNAmicroarrayschemacDNA晶片製造原理MicroarrayanalysisOperationPrinciple:Samplesaretaggedwithflourescentmaterialtoshowpatternofsample-probeinteraction(hybridization)Microarraymayhave60KprobeMicroarrayProcessingsequenceFrom:Shin-MuTsengGene-expressionprofilingbymeansofmicroarraysandreverse-transcriptasepolymerasechainreaction(RT-PCR)examinedgeneexpressionin125surgicalspecimensofNSCLC,usingmicroarraysandreal-timeRT-PCRtoidentifyagenesignaturecorrelatedwithclinicaloutcomeMethodscomputer-generatedrandomnumberstoassignspecimensfrom185consecutivepatientsformicroarrayanalysisfrozenspecimensoflung-cancertissuefrom125randomlyselectedpatientswhounderwentsurgicalresectionofNSCLCatTaichungVeteransGeneralHospitalbetweenDecember2023andDecember2023------five-generisk-predictionmodelusinganindependentcohortof60randomlyselectedpatients125specimens--60wereadenocarcinomas,52weresquamous-cellcarcinomas,and13wereothertypesofcancernotreceivedadjuvantchemotherapy672genesassociatedwithinvasiveactivity,identifiedinapreviousstudy---rearrayedinduplicateonanylonmembrane4μgoftotalRNAfromeachspecimenvalidatelevelsofexpressionofgenesfoundonmicroarrayanalysisRT-PCRwasperformedon16genesandacontrolgeneforTATA-box–bindingprotein(TBP),withuseofspecificTaqManprobesandprimersets---transcriptswereamplifiedwithreagent(TaqManOne-StepRT-PCRMasterMixReagent,AppliedBiosystems)andasequencedetectionsystem(ABIPrism7900HT,AppliedBiosystems)Toreducebackgroundnoisebackgroundintensityvaluesoflessthan3000wereassignedvalueof3000log-transformedtoabase-2scaleGeneswithcoefficientsofvariationoflessthan3%wereexcludedfromfurtheranalysesthegene-expressionintensityvaluesweretransformedtoordinalcodingvaluesbyrankingoflevelofgeneexpressionamongthe485genesin125patients(60,625observations)intensityvaluewascodedas1-2-3-4accordingto0-25%-50%-75%-100%HazardratiosfromunivariateCoxregressionanalysistodeterminewhichgenesassociatedwithdeathfromanycauseorrecurrenceofcancerProtectivegenesweredefinedwithahazardratiofordeathof<1;riskgenesweredefinedwithahazardratiofordeathof>1univariateCoxproportional-hazardsregressionanalysisGenessignificantlycorrelatedwithsurvival---alinearcombinationofgene-expressioncodingvaluesweightedbyregressioncoefficientstocalculateariskscoreforeachpatientpatient’sriskscorewascalculatedassumoflevelsofexpressionofeachgene,asmeasuredbymicroarrayanalysis,multipliedbycorrespondingregressioncoefficientshigh-riskgenesignatureoralow-riskgenesignature,with50thpercentile(median)oftheriskscoreasthethresholdvalue(median,4.9;range,1.3to21.9)---thresholdvaluetoreflectalmosthalfofpatientswithearlystageNSCLCrelapsewithin5yearsafterpotentiallycurativesurgery,eliminateeffectofextremevalueslevelsofexpressionof16genesconfirmedbyRT-PCRandindexedbySpearman’srank-correlationtestfurtheridentified5genessignificantlyassociatedwithsurvivalrecursive-partitioningdecisiontree&Avadissoftware(StrandGenomic)ahigh-riskgenesignatureoralow-riskgenesignatureKaplan–Meiermethodtoestimateoverallsurvivalandrelapse-freesurvivalMultivariateCoxproportionalhazardsregressionanalysiswithstepwiseselectionevaluateindependentprognosticfactorswithsurvival,5-genesignature,age,sex,tumorstage,andhistologiccharacteristicsascovariatesTofurthervalidateourmodel,weappliedittomicroarraydatafrom86patientswithNSCLC,reportedbyBeeretalfivegenes(andtheircorrespondingAffymetrixprobesets)wereDUSP6(X93920at),MMD(X85750at),STAT1(M97936at),ERBB3(S61953at),andLCK(M26692sat);thecontrolgenewasTBP(X54993sat)maximumfollow-uptimeforsurvivalanalysisinourstudywas62months,weused5-yearsurvivaldatafor86patientsResults

16genescorrelatedwithdeathfromanycause:4wereprotectivegenes(hazardratio<1)and12wereriskgenes(hazardratio>1)dual-specificityphosphatase6(DUSP6)

monocyte-to-macrophagedifferentiationassociatedprotein(MMD)signaltransducerandactivatoroftranscription1(STAT1)v-erb-b2avianerythroblasticleukemiaviraloncogenehomolog3(ERBB3)lymphocyte-specificproteintyrosinekinase(LCK)5-genesignaturestronglyassociatedwithoverallsurvival(sensitivity,98%;specificity,93%;positivepredictivevalue,95%;negativepredictivevalue,98%;andoverallaccuracy,96%)AmongpatientswithstageIIdisease,overallsurvivaldidnotdiffersignificantlybetweenhigh-riskandlow-riskgenesignatures,probablyowingtosmallnumberofpatientsDiscussion

NSCLCisaheterogeneousdiseasebasedonclinicalandpathologicalfindingsmayhavelimitofusefulnessforpredictingoutcomes,butmolecularmethodsaddvalueuseofmicroarraysinclinicalpracticelimitedbythelargenumberofgenesintheanalysis,complicatedmethods,lackofreproducibilityandindependentvalidationofresults,andneedforfresh-frozentissueRT-PCRinvolvingasmallnumberofgenesallowsforaccurateandreproduciblequantificationofresultsforRNAobtainedfromsmallamountsofparaffin-embeddedspecimens125frozentumorspecimensfrompatientswithNSCLCrandomlydividedintoatrainingset(63specimens)andatestingset(62specimens)selectionofgenesinmicroarraytrainingsetwasvalidatedinmicroarraytestingset,andpatternsofgeneexpressionfoundonmicroarrayanalysiswerevalidatedbyRT-PCRresultsinourChinesepatientswerealsovalidatedwithuseofasetofpublishedNSCLCmicroarraydatafrompatientsfromaWesternpopulationwithNSCLCproposewhohavetumorswithahigh-riskgenesignaturecouldbenefitfromCisplatin-basedadjuvantchemotherapy,thosewithalow-riskgenesignaturecouldbespared---large-scale,multicenterstudiesarenecessarytotestthisideaSTAT1arrestedgrowthandapoptosisinmanytypesofcancercellsbyinducingexpressionofp21WAF1andcaspase.MMDexpressedinmaturemacrophages,macrophageactivationpromotescancermetastasis,BUTfunctionofMMDproteinisunknownDUSP6inactivatesextracellularsignal-regulatedkinase2(ERK2)(alsoknownasmitogen-activatedproteinkinase1[MAPK1]),resultingintumorsuppressionandapoptosisERBB3memberofepidermalgrowthfactorreceptorfamilyoftyrosinekinases,canshortencellsurvivalLCKmemberoftheSrcfamilyofproteintyrosinekinases,isexpressedmainlyinTcellsandisoneoffirstsignalingmoleculesdownstreamoftheT-cellreceptor,akeyrolenotonlyindifferentiationandactivationofTcellsbutalsoininductionofapoptosis;LCKisexpressedinmanycancersandregulatesmobilityofcancercells5-GenecanpredictclinicaloutcomeinpatientswithsurgicallyresectedNSCLC.ThissignaturecouldbeusefulinstratifyingpatientsaccordingtoriskintrialsofadjuvanttreatmentofthediseaseThankyouforyourattention!!!企业分配决策

第一节企业分配的基本理论

一.企业分配的含义

企业分配是根据企业所有权的归属及各权益占有的比例,对企业生产成果进行划分,是一种利用财务手段确保生产成果的合理归属和正确分配的管理过程。企业分配是对企业一定生产成果的分配。



利润是指企业在一定时期内从事各种经营活动所获取的经营成果。企业的利润总额由营业利润、投资净收益、补贴收入和营业外收支净额组成。

补贴收入指企业按规定实际收到退还的增值税或按销量或工作量等依据国家规定的补助定额计算并按期给予的定额补贴及属于国家扶持的领域而给予的其他形式的补贴。

(一)营业利润：是企业通过销售商品和提供劳务等经营业务实现的利润。

营业利润=营业收入-营业成本-期间费用

营业收入:指企业通过销售商品和提供劳务等经营业务实现的收入。

营业成本:指企业为生产,销售商品和提供劳务等发生的直接人工、直接材料、制造费用等。

期间费用:是直接计入当期损益的费用。包括管理费用,财务费用和营业费用。(二)投资净收益：是指企业对外投资收益扣除投资损失后的数额。

投资收益:投资股票分得的股利,投资债券取得的利息收入,从被投资企业分得的利润,投资到期收回的款项或中途转让取得的款项高于投资账面价值的差额。

投资损失:指投资到期收回的款项或中途转让取的款项低于投资账面价值的差额。(三)营业外收支：指与企业生产经营无直接联系的收入和支出。

营业外收入:固定资产盘盈净收入、出售固定资产净收益、对方违约的赔款收入等。

营业外支出:固定资产盘亏、报废毁损和出售的净损失、非常损失、公益救济性捐款、赔偿金、违约金等。主营业务利润=

主营业务收入-主营业务成本

-主营业务税金及附加

营业利润=

主营业务利润+其他业务利润

-管理费用-营业费用-财务费用

利润总额=

营业利润+投资收益+营业外收入

-营业外支出+补贴收入

净利润=利润总额-所得税二.企业分配原则

（一）发展优先原则

正确处理积累与消费的关系

防止两种错误倾向：

★积累的比例太大★