Three-gene prognostic classifier for early-stage non small-cell lung cancer.
OBJECTIVE
Several microarray studies have reported gene expression signatures that classify non-small-cell lung carcinoma (NSCLC) patients into different prognostic groups. However, the prognostic gene lists reported to date overlap poorly across studies, and few have been validated independently using more quantitative assay methods.


METHODS
The expression of 158 putative prognostic genes identified in previous microarray studies was analyzed by reverse transcription quantitative polymerase chain reaction in the tumors of 147 NSCLC patients. Concordance indices and risk scores were used to identify a stage-independent set of genes that could classify patients with significantly different prognoses.


RESULTS
We have identified a three-gene classifier (STX1A, HIF1A, and CCR7) for overall survival (hazard ratio = 3.8; 95% CI, 1.7 to 8.2; P < .001). The classifier was also able to stratify stage I and II patients and further improved the predictive ability of clinical factors such as histology and tumor stage. The predictive value of this three-gene classifier was validated in two large independent microarray data sets from Harvard and Duke Universities.


CONCLUSIONS
We have identified a new three-gene classifier that is independent of and improves on stage to stratify early-stage NSCLC patients with significantly different prognoses. This classifier may be tested further for its potential value to improve the selection of resected NSCLC patients in adjuvant therapy.
Lau
Suzanne K
SK
Princess Margaret Hospital, 610 University Ave, Toronto, Ontario, Canada.
Boutros
Paul C
PC
Pintilie
Melania
M
Blackhall
Fiona H
FH
Zhu
Chang-Qi
CQ
Strumpf
Dan
D
Johnston
Michael R
MR
Darling
Gail
G
Keshavjee
Shaf
S
Waddell
Thomas K
TK
Liu
Ni
N
Lau
Davina
D
Penn
Linda Z
LZ
Shepherd
Frances A
FA
Jurisica
Igor
I
Der
Sandy D
SD
Tsao
Ming-Sound
MS
D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005820:Genetic Testing / Q000592:standards; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D054400:Receptors, CCR7 / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000592:standards; D050827:Syntaxin 1 / Q000032:analysis*
D014408:Biomarkers, Tumor; C515370:CCR7 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D054400:Receptors, CCR7; C494212:STX1A protein, human; D050827:Syntaxin 1