Data from The Expression of Four Genes as a Prognostic Classifier for Stage I Lung Adenocarcinoma in 12 Independent Cohorts

Abstract

<div>Abstract<p><b>Background:</b> We previously developed a prognostic classifier using the expression levels of <i>BRCA1, HIF1A, DLC1</i>, and <i>XPO1</i> that identified stage I lung adenocarcinoma patients with a high risk of relapse. That study evaluated patients in five independent cohorts from various regions of the world. In an attempt to further validate the classifier, we have used a meta-analysis–based approach to study 12 cohorts consisting of 1,069 tumor–node–metastasis stage I lung adenocarcinoma patients from every suitable, publically available dataset.</p><p><b>Methods:</b> Cohorts were obtained through a systematic search of public gene expression datasets. These data were used to calculate the risk score using the previously published 4-gene risk model. A fixed effect meta-analysis model was used to generate a pooled estimate for all cohorts.</p><p><b>Results:</b> The classifier was associated with prognosis in 10 of the 12 cohorts (<i>P</i> < 0.05). This association was highly consistent regardless of the ethnic diversity or microarray platform. The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I [HR, 2.66; 95% confidence interval (CI), 1.93–3.67; <i>P</i> < 0.0001] patients and in stratified analyses of stage IA (HR, 2.69; 95% CI, 1.66–4.35; <i>P</i> < 0.0001) and stage IB (HR, 2.69; 95% CI, 1.74–4.16; <i>P</i> < 0.0001) patients.</p><p><b>Conclusions:</b> The 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors.</p><p><b>Impact:</b> Our results suggest that the 4-gene classifier may assist clinicians in decisions about the postoperative management of early-stage lung adenocarcinoma patients. <i>Cancer Epidemiol Biomarkers Prev; 23(12); 2884–94. ©2014 AACR</i>.</p></div>