title: Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung.
abstract: OBJECTIVE
  Adjuvant treatment may improve survival in early-stage squamous cell carcinoma (SCC) of the lung; however, the absolute gain is modest and mainly limited to stage II-IIIA. Current staging methods are imprecise indications of prognosis, but high-risk patients can be identified by gene expression profiling and considered for adjuvant therapy.
  
  
  METHODS
  The expression of 29 genes was assessed by reverse transcriptase quantitative PCR in frozen primary tumor specimens obtained from 66 SCC patients who had undergone surgical resection. Expression values were dichotomized using the median as a cutoff value. We used a risk score to develop a gene expression model for the prediction of survival.
  
  
  RESULTS
  The univariate analysis of gene expression in the training cohort identified 10 genes with significant prognostic value: CSF1, EGFR, CA IX, PH4, KIAA0974, ANLN, VEGFC, NTRK1, FN1, and INR1. In the multivariate Cox model, CSF1 (hazard ratio, 3.5; P = 0.005), EGFR (hazard ratio, 2.7; P = 0.02), CA IX (hazard ratio, 0.2; P < 0.0001), and tumor size >4 cm (hazard ratio, 2.7; P = 0.02) emerged as significant markers for survival. The high prognostic value of a risk score based on the expression of the three genes (CSF1, EGFR, and CA IX) was positively validated in a separate cohort of 26 patients in an independent laboratory (P = 0.05).
  
  
  CONCLUSIONS
  The three-gene signature is strongly associated with prognosis in early-stage SCC. Positive independent validation suggests its suitability for selecting SCC patients with an increased risk of death who might benefit from adjuvant treatment.
authors.affiliation: University of Gdansk, Gdansk, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Skrzypski
authors.forename: Ewa
authors.initials: E
authors.lastname: Jassem
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Pedro
authors.initials: P
authors.lastname: Mendez
authors.forename: Witold
authors.initials: W
authors.lastname: Rzyman
authors.forename: Grazyna
authors.initials: G
authors.lastname: Gulida
authors.forename: Dan
authors.initials: D
authors.lastname: Raz
authors.forename: David
authors.initials: D
authors.lastname: Jablons
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: Imane
authors.initials: I
authors.lastname: Chaib
authors.forename: Laia
authors.initials: L
authors.lastname: Perez-Roca
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D016173:Macrophage Colony-Stimulating Factor; D066246:ErbB Receptors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases