Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.
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.
Department of Statistics, 1085 South University, University of Michigan, Ann Arbor, Michigan 48109, USA.
Shedden
Kerby
K
Taylor
Jeremy M G
JM
Enkemann
Steven A
SA
Tsao
Ming-Sound
MS
Yeatman
Timothy J
TJ
Gerald
William L
WL
Eschrich
Steven
S
Jurisica
Igor
I
Giordano
Thomas J
TJ
Misek
David E
DE
Chang
Andrew C
AC
Zhu
Chang Qi
CQ
Strumpf
Daniel
D
Hanash
Samir
S
Shepherd
Frances A
FA
Ding
Keyue
K
Seymour
Lesley
L
Naoki
Katsuhiko
K
Pennell
Nathan
N
Weir
Barbara
B
Verhaak
Roel
R
Ladd-Acosta
Christine
C
Golub
Todd
T
Gruidl
Michael
M
Sharma
Anupama
A
Szoke
Janos
J
Zakowski
Maureen
M
Rusch
Valerie
V
Kris
Mark
M
Viale
Agnes
A
Motoi
Noriko
N
Travis
William
W
Conley
Barbara
B
Seshan
Venkatraman E
VE
Meyerson
Matthew
M
Kuick
Rork
R
Dobbin
Kevin K
KK
Lively
Tracy
T
Jacobson
James W
JW
Beer
David G
DG
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