Sample-level enrichment analysis unravels shared stress phenotypes among multiple cancer types 英文参考文献.docVIP

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Sample-level enrichment analysis unravels shared stress phenotypes among multiple cancer types 英文参考文献.doc

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Sample-level enrichment analysis unravels shared stress phenotypes among multiple cancer types 英文参考文献

GundemandLopez-BigasGenomeMedicine2012,4:28 /content/4/3/28 RESEARCH OpenAccess Sample-levelenrichmentanalysisunravelsshared stressphenotypesamongmultiplecancertypes GunesGundem1,2* andNuriaLopez-Bigas1,3* Abstract Background:Adaptationtostresssignalsinthetumormicroenvironmentisacrucialsteptowardscarcinogenic phenotype.Theadaptivealterationsattainedbycellstowithstanddifferenttypesofinsultsarecollectivelyreferred toasthestressphenotypesofcancers.Inthismanuscriptweexploretheinterrelationofdifferentstress phenotypesinmultiplecancertypesandaskifthesephenotypescouldbeusedtoexplainprognosticdifferences amongtumorsamples. Methods:Weproposeanewapproachbasedonenrichmentanalysisatthelevelofsamples(sample-level enrichmentanalysis-SLEA)inexpressionprofilingdatasets.Withoutusingaprioriphenotypicinformationabout samples,SLEAcalculatesanenrichmentscorepersamplepergenesetusingz-test.Thisscoreisusedtodetermine therelativeimportanceofthecorrespondingpathwayormoduleindifferentpatientgroups. Results:Ouranalysisshowsthattumorssignificantlyupregulatinggenesrelatedtochromosomeinstability stronglycorrelatewithworseprognosisinbreastcancer.Moreover,inmultipletumortypes,thesetumors upregulateasenescence-bypasstranscriptionalprogramandexhibitsimilarstressphenotypes. Conclusions:UsingSLEAweareabletofindrelationshipsbetweenstressphenotypepathwaysacrossmultiple cancertypes.MoreoverweshowthatSLEAenablestheidentificationofgenesetsincorrelationwithclinical characteristicssuchassurvival,aswellastheidentificationofbiologicalpathways/processesthatunderliethe pathologyofdifferentcancersubgroups. Background methodologies are based on the idea that analysis of Complexgeneticdiseases suchascancerarecharacter- pathway-leveldifferencesamongsamplescouldhavean izedbyphenotypicheterogeneity reflected atthemole- advantage of reflecting the true oncogenic phenotypes cular level in the form of variations in the activity of achievedthroughconsistentexpressionofasetofgenes certain signaling pathways. In su