title: A four-gene signature from NCI-60 cell line for survival prediction in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Yi-Chiung
authors.initials: YC
authors.lastname: Hsu
authors.forename: Shinsheng
authors.initials: S
authors.lastname: Yuan
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Liu
authors.forename: Pin-Yen
authors.initials: PY
authors.lastname: Hsu
authors.forename: Guani
authors.initials: G
authors.lastname: Wu
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Ker-Chau
authors.initials: KC
authors.lastname: Li
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: 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
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen