Validation of 5- and 3-gene expression signatures for predicting outcome in non-small cell lung cancer (NSCLC) patients (p).

7532 Background: A number of prognostic gene expression signatures have been reported to predict survival in lung cancer, including a 5-gene signature (Chen et al, N Engl J Med 2007) and a 3-gene signature in squamous cell carcinoma (SCC) (Skrzypski et al. ASCO 2007). We have examined these two signatures in tumors from 142 NSCLC p.,From 2000 to 2005, freshly frozen primary tumor specimens were obtained at the time of surgery from 142 NSCLC p (80% stage I and II; 66% SCC, 33% adenocarcinomas). Expression of genes included in the 5-gene signature (MMD, ERBB3, LCK, STAT1, DUSP6) and the 3-gene signature (CSF1, EGFR, CA IX) was assessed by quantitative RT-PCR in low density arrays, using TBP as endogenous control. Risk scores were used to classify p into high- or low-risk according to the expression of the genes in the two signatures.,All genes included in the 5-gene signature were more highly expressed in adenocarcinoma than in SCC, leading us to adjust the risk score for histology. According to the original risk score for the 5-gene signature, median survival (MS) for low-risk p was not reached while it was 29.7 months (m) for high-risk p (P=0.22). However, using the adjusted risk score for SCC, MS for low-risk p was 63 m vs 24 m for high-risk p (P=0.003). Using the adjusted risk score for adenocarcinoma, MS for low-risk p was not reached, while it was 46.2 m for high-risk p (P=0.006). According to the risk score for the 3-gene signature, MS for high-risk p was 41 m vs 62.4 m for low-risk p (P=0.009). For stage I-II SCC p, MS in low-risk p was not reached, while it was 34 m for high-risk p (P=0.05). For adenocarcinoma p, MS was not reached for low-risk p, while it was 61.2 m for high-risk p (P=0.04).,The 5-gene signature is highly predictive of survival when adjusted for histology. The 3-gene signature is predictive of survival without adjustment for histology. These gene signatures can be useful for selecting high-risk p for adjuvant chemotherapy. No significant financial relationships to disclose.