title: Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.
abstract: Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) could be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early-stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas.
authors.affiliation: Department of Statistics, 1085 South University, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Kerby
authors.initials: K
authors.lastname: Shedden
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.forename: Steven A
authors.initials: SA
authors.lastname: Enkemann
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Yeatman
authors.forename: William L
authors.initials: WL
authors.lastname: Gerald
authors.forename: Steven
authors.initials: S
authors.lastname: Eschrich
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.forename: David E
authors.initials: DE
authors.lastname: Misek
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chang
authors.forename: Chang Qi
authors.initials: CQ
authors.lastname: Zhu
authors.forename: Daniel
authors.initials: D
authors.lastname: Strumpf
authors.forename: Samir
authors.initials: S
authors.lastname: Hanash
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naoki
authors.forename: Nathan
authors.initials: N
authors.lastname: Pennell
authors.forename: Barbara
authors.initials: B
authors.lastname: Weir
authors.forename: Roel
authors.initials: R
authors.lastname: Verhaak
authors.forename: Christine
authors.initials: C
authors.lastname: Ladd-Acosta
authors.forename: Todd
authors.initials: T
authors.lastname: Golub
authors.forename: Michael
authors.initials: M
authors.lastname: Gruidl
authors.forename: Anupama
authors.initials: A
authors.lastname: Sharma
authors.forename: Janos
authors.initials: J
authors.lastname: Szoke
authors.forename: Maureen
authors.initials: M
authors.lastname: Zakowski
authors.forename: Valerie
authors.initials: V
authors.lastname: Rusch
authors.forename: Mark
authors.initials: M
authors.lastname: Kris
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.forename: Noriko
authors.initials: N
authors.lastname: Motoi
authors.forename: William
authors.initials: W
authors.lastname: Travis
authors.forename: Barbara
authors.initials: B
authors.lastname: Conley
authors.forename: Venkatraman E
authors.initials: VE
authors.lastname: Seshan
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Dobbin
authors.forename: Tracy
authors.initials: T
authors.lastname: Lively
authors.forename: James W
authors.initials: JW
authors.lastname: Jacobson
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D000465:Algorithms; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve; D012306:Risk; D016896:Treatment Outcome