title: Gene expression-based classification of non-small cell lung carcinomas and survival prediction.
abstract: BACKGROUND
  Current clinical therapy of non-small cell lung cancer depends on histo-pathological classification. This approach poorly predicts clinical outcome for individual patients. Gene expression profiling holds promise to improve clinical stratification, thus paving the way for individualized therapy.
  
  
  RESULTS
  A genome-wide gene expression analysis was performed on a cohort of 91 patients. We used 91 tumor- and 65 adjacent normal lung tissue samples. We defined sets of predictor genes (probe sets) with the expression profiles. The power of predictor genes was evaluated using an independent cohort of 96 non-small cell lung cancer- and 6 normal lung samples. We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of non-small cell lung cancer. Correlation analysis identified 17 genes which showed the best association with post-surgery survival time. This signature was used for stratification of all patients in two risk groups. Kaplan-Meier survival curves show that the two groups display a significant difference in post-surgery survival time (p = 5.6E-6). The performance of the signatures was validated using a patient cohort of similar size (Duke University, n = 96). Compared to previously published prognostic signatures for NSCLC, the 17 gene signature performed well on these two cohorts.
  
  
  CONCLUSIONS
  The gene signatures identified are promising tools for histo-pathological classification of non-small cell lung cancer, and may improve the prediction of clinical outcome.
authors.affiliation: Cell Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Joachim
authors.initials: J
authors.lastname: Aerts
authors.forename: Bianca
authors.initials: B
authors.lastname: den Hamer
authors.forename: Wilfred
authors.initials: W
authors.lastname: van Ijcken
authors.forename: Michael
authors.initials: M
authors.lastname: den Bakker
authors.forename: Peter
authors.initials: P
authors.lastname: Riegman
authors.forename: Cor
authors.initials: C
authors.lastname: van der Leest
authors.forename: Peter
authors.initials: P
authors.lastname: van der Spek
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016571:Neural Networks, Computer; D057285:Precision Medicine / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis; D015996:Survival Rate
chemical_list: D012334:RNA, Neoplasm