Validation of a Histology-Independent Prognostic Gene Signature for Early-Stage, Non–Small-Cell Lung Cancer Including Stage IA Patients

Abstract

Patients with early-stage non-small-cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial. In this study, we assessed its value in an independent set of cases. Expression profiling was performed on RNA from frozen, resected tumor tissues corresponding to 181 stage I and II NSCLC cases collected at University Health Network (UHN181). Kaplan-Meier methodology was used to estimate 5-year overall survival probabilities, and the prognostic effect of the classifier was assessed using the log-rank test. A Cox proportional hazards model evaluated the signature's effect adjusting for clinical prognostic factors. Expression data of the 15-gene classifier stratified UHN181 cases into high- and low-risk subgroups with significantly different overall survival (hazard ratio [HR] = 1.92; 95% confidence interval [CI], 1.15-3.23; p = 0.012). In a subgroup analysis, this classifier predicted survival in 127 stage I patients (HR = 2.17; 95% CI, 1.12-4.20; p = 0.018) and the smaller subgroup of 48 stage IA patients (HR = 5.61; 95% CI, 1.19-26.45; p = 0.014). The signature was prognostic for both adenocarcinoma and squamous cell carcinoma cases (HR = 1.76, p = 0.058; HR = 4.19, p = 0.045, respectively). The prognostic accuracy of a 15-gene classifier was validated in an independent cohort of 181 early-stage NSCLC samples including stage IA cases and in different NSCLC histologic subtypes.