基于通路的癌癥遺傳異質(zhì)性研究方法.pdf

1、中山大學(xué)碩士學(xué)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(qǐng)學(xué)位級(jí)別：碩士專業(yè)：運(yùn)籌學(xué)與控制論指導(dǎo)教師：黃煜饒紹奇20100529中山大學(xué)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