基于通路的癌癥遺傳異質(zhì)性研究方法.pdf

1、中山大學碩士學位論文基于通路的癌癥遺傳異質(zhì)性研究方法姓名：趙小蕾申請學位級別：碩士專業(yè)：運籌學與控制論指導教師：黃煜饒紹奇20100529中山大學碩士生論文Title：aMethodofPeelingofftheHiddenGeneticHeterogeneitiesofCancersBasedonPathwayMajor：operationalresearchandcyberneticsName：ZhaoXiaoleiSupervis

2、or：ProfHuangYu，RaoShaoqiABSTRACTDiscoveringthesubtypesofcancerinmolecularlevelisofcriticalimportancebothforunderstandingpathogenicmechanismsandforfindingefficienttreatmentsRecentlyithasbeenrecognizedthehiddengeneticheter

3、ogeneitiesofcancersarerelatedtopmhwaySothegeneshighlyⅦriablyexpressedacrossthediseasesamplesthataresignificantlyenrichinthesamepathwayshouldhelptounravelthehiddensubtypesofcancerTheywerefinallyusedtodiscoverthesubtypesof

4、cancerbyclusteringalgorithmAsforvalidationweusedalargecancerdatasettoevaluatetheabilityofthemethodofpeelingoffthehiddengeneticheterogeneitiesofcancersbasedonpathwayforcorrectlyportioningsamplesThenweappliedtheproposedmet

5、hodtotwopubliclyavailablemicroarraydatasetsofdiffuselargeBcelllymphoma(DLBCL)，anotoriouslyheterogeneousphenotypeFinallytheclinicalsignificanceoftheidentifiedsubtypeswasverifiedbysurvivalanalysisInthevalidationdataset，wea

6、chievedhighlyaccuratepartitionsthatbestfittheclinicalcancerphenotypesThen，forthetwonotoriouslyheterogeneousDLBCL，wehadtheexcellentresultsOneofthemdemonstratethattwopartitionedsubtypesusingthefunctionalgenegroupshadverydi

7、fferent5yearoverallrates(62％，24％)andwerehighlysignificantly(p=o024)correlatedwiththeclinicalsurvivalrate，andtheotherdemonstratethatthreepartitionedsubtypeshadverydifferent10一yearoverallrates(90％，46％，20％)andwerehighlysign