Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung.
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.
Skrzypski
Marcin
M
University of Gdansk, Gdansk, Poland.
Jassem
Ewa
E
Taron
Miquel
M
Sanchez
Jose Javier
JJ
Mendez
Pedro
P
Rzyman
Witold
W
Gulida
Grazyna
G
Raz
Dan
D
Jablons
David
D
Provencio
Mariano
M
Massuti
Bartomeu
B
Chaib
Imane
I
Perez-Roca
Laia
L
Jassem
Jacek
J
Rosell
Rafael
R
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
D000951:Antigens, Neoplasm; D016173:Macrophage Colony-Stimulating Factor; D066246:ErbB Receptors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases