A five-gene signature and clinical outcome in non-small-cell lung cancer.
BACKGROUND
Current staging methods are inadequate for predicting the outcome of treatment of non-small-cell lung cancer (NSCLC). We developed a five-gene signature that is closely associated with survival of patients with NSCLC.


METHODS
We used computer-generated random numbers to assign 185 frozen specimens for microarray analysis, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, or both. We studied gene expression in frozen specimens of lung-cancer tissue from 125 randomly selected patients who had undergone surgical resection of NSCLC and evaluated the association between the level of expression and survival. We used risk scores and decision-tree analysis to develop a gene-expression model for the prediction of the outcome of treatment of NSCLC. For validation, we used randomly assigned specimens from 60 other patients.


RESULTS
Sixteen genes that correlated with survival among patients with NSCLC were identified by analyzing microarray data and risk scores. We selected five genes (DUSP6, MMD, STAT1, ERBB3, and LCK) for RT-PCR and decision-tree analysis. The five-gene signature was an independent predictor of relapse-free and overall survival. We validated the model with data from an independent cohort of 60 patients with NSCLC and with a set of published microarray data from 86 patients with NSCLC.


CONCLUSIONS
Our five-gene signature is closely associated with relapse-free and overall survival among patients with NSCLC.
Chen
Hsuan-Yu
HY
National Taiwan University College of Public Health, National Taiwan University College of Medicine, Taipei, Taiwan.
Yu
Sung-Liang
SL
Chen
Chun-Houh
CH
Chang
Gee-Chen
GC
Chen
Chih-Yi
CY
Yuan
Ang
A
Cheng
Chiou-Ling
CL
Wang
Chien-Hsun
CH
Terng
Harn-Jing
HJ
Kao
Shu-Fang
SF
Chan
Wing-Kai
WK
Li
Han-Ni
HN
Liu
Chun-Chi
CC
Singh
Sher
S
Chen
Wei J
WJ
Chen
Jeremy J W
JJ
Yang
Pan-Chyr
PC
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D003663:Decision Trees; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D016019:Survival Analysis