Publication
An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non–Small-Cell Lung Cancer
Publisher:
American Association for Cancer Research (AACR)
Date:
31-12-2008
DOI:
10.1158/1078-0432.CCR-08-1258
Abstract: Purpose: Current staging methods are imprecise for predicting prognosis of early-stage non–small-cell lung cancer (NSCLC). We aimed to develop a gene expression profile for stage I and stage II NSCLC, allowing identification of patients with a high risk of disease recurrence within 2 to 3 years after initial diagnosis. Experimental Design: We used whole-genome gene expression microarrays to analyze frozen tumor s les from 172 NSCLC patients (pT1-2, N0-1, M0) from five European institutions, who had undergone complete surgical resection. Median follow-up was 89 months (range, 1.2-389) and 64 patients developed a recurrence. A random two thirds of the s les were assigned as the training cohort with the remaining s les set aside for independent validation. Cox proportional hazards models were used to evaluate the association between expression levels of in idual genes and patient recurrence-free survival. A nearest mean analysis was used to develop a gene-expression classifier for disease recurrence. Results: We have developed a 72-gene expression prognostic NSCLC classifier. Based on the classifier score, patients were classified as either high or low risk of disease recurrence. Patients classified as low risk showed a significantly better recurrence-free survival both in the training set (P & 0.001 n = 103) and in the independent validation set (P & 0.01 n = 69). Genes in our prognostic signature were strongly enriched for genes associated with immune response. Conclusions: Our 72-gene signature is closely associated with recurrence-free and overall survival in early-stage NSCLC patients and may become a tool for patient selection for adjuvant therapy.