A four-gene signature from NCI-60 cell line for survival prediction in non-small cell lung cancer.
OBJECTIVE
Metastasis is the main cause of mortality in non-small cell lung cancer (NSCLC) patients. Genes that can discriminate the invasion ability of cancer cells may become useful candidates for clinical outcome prediction. We identify invasion-associated genes through computational and laboratorial approach that supported this idea in NSCLC.


METHODS
We first conducted invasion assay to characterize the invasion abilities of NCI-60 lung cancer cell lines. We then systematically exploited NCI-60 microarray databases to identify invasion-associated genes that showed differential expression between the high and the low invasion cell line groups. Furthermore, using the microarray data of Duke lung cancer cohort (GSE 3141), invasion-associated genes with good survival prediction potentials were obtained. Finally, we validated the findings by conducting quantitative PCR assay on an in-house collected patient group (n = 69) and by using microarray data from two public western cohorts (n = 257 and 186).


RESULTS
The invasion-associated four-gene signature (ANKRD49, LPHN1, RABAC1, and EGLN2) had significant prediction in three validation cohorts (P = 0.0184, 0.002, and 0.017, log-rank test). Moreover, we showed that four-gene signature was an independent prognostic factor (hazard ratio, 2.354, 1.480, and 1.670; P = 0.028, 0.014, and 0.033), independent of other clinical covariates, such as age, gender, and stage.


CONCLUSIONS
The invasion-associated four-gene signature derived from NCI-60 lung cancer cell lines had good survival prediction power for NSCLC patients.
Hsu
Yi-Chiung
YC
Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, Republic of China.
Yuan
Shinsheng
S
Chen
Hsuan-Yu
HY
Yu
Sung-Liang
SL
Liu
Chia-Hsin
CH
Hsu
Pin-Yen
PY
Wu
Guani
G
Lin
Chia-Hung
CH
Chang
Gee-Chen
GC
Li
Ker-Chau
KC
Yang
Pan-Chyr
PC
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015331:Cohort Studies; D003094:Collagen / Q000737:chemistry; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011509:Proteoglycans / Q000737:chemistry; D016896:Treatment Outcome
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen