Early Detection of Malignant Pleural Mesothelioma in Asbestos-Exposed Individuals with a Noninvasive Proteomics-Based Surveillance Tool 英文参考文献.docVIP
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Early Detection of Malignant Pleural Mesothelioma in Asbestos-Exposed Individuals with a Noninvasive Proteomics-Based Surveillance Tool 英文参考文献
EarlyDetectionofMalignantPleuralMesotheliomain
Asbestos-ExposedIndividualswithaNoninvasive
Proteomics-BasedSurveillanceTool
RachelM.Ostroff1*.,MichaelR.Mehan1.,AlexStewart1,DeborahAyers1,EdwardN.Brody1,
StephenA.Williams1,StephenLevin2,BradBlack3,MichaelHarbut4,MicheleCarbone5,
ChandraGoparaju6,HarveyI.Pass6
1ClinicalResearch,SomaLogicInc.,Boulder,Colorado,UnitedStatesofAmerica,2CenterforOccupationalandEnvironmentalMedicine,Mt.SinaiMedicalCenter,New
York,NewYork,UnitedStatesofAmerica,3CenterforAsbestosRelatedDiseases,Libby,Montana,UnitedStatesofAmerica,4EnvironmentalCancerProgram,Karmanos
CancerCenter,Detroit,Michigan,UnitedStatesofAmerica,5DepartmentofPathology,CancerResearchCenterofHawaii,Honolulu,Hawaii,UnitedStatesofAmerica,
6DepartmentofCardiothoracicSurgery,NewYorkUniversityLangoneMedicalCenterandCancerCenter,NewYork,NewYork,UnitedStatesofAmerica
Abstract
Background:Malignantpleuralmesothelioma(MM)isanaggressive,asbestos-relatedpulmonarycancerthatisincreasing
inincidence.Becausediagnosisisdifficultandthediseaseisrelativelyrare,mostpatientspresentataclinicallyadvanced
stagewherepossibility ofcure isminimal. Toimprove surveillanceanddetectionof MM inthehigh-risk population,we
completedaseriesofclinicalstudiestodevelopanoninvasivetestforearlydetection.
Methodology/PrincipalFindings:Weconductedmulti-centercase-controlstudiesinserumfrom117MMcasesand142
asbestos-exposed control individuals. Biomarker discovery, verification, and validation were performed using SOMAmer
proteomic technology, which simultaneously measures over 1000 proteins in unfractionated biologic samples. Using
univariateandmultivariateapproacheswediscovered64candidateproteinbiomarkersandderiveda13-markerrandom
forest classifier with an AUC of 0.9960.01 in training, 0.9860.04 in independent blinded verification and 0.9560.04 in
blindedvalidationstudies.Sensitivityandspecificityatourpre-specifieddecisionthresholdwere97%/92%intrainingand
90%/95%inblindedverification.Thisclassifieraccuracywasmain
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