The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts
Menée à partir de données portant sur 12 cohortes incluant au total 1 069 patients atteints d'un adénocarcinome du poumon de stade I, cette étude évalue l'association entre un outil de classification, basé sur les niveaux d'expression de 4 gènes (BRCA1, HIF1A, DLC1 et XPO1), et la survie globale des patients
Background : We previously developed a prognostic classifier using the expression levels of BRCA1, HIF1A, DLC1, and XPO1 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 1069 TNM stage I lung adenocarcinoma patients from every suitable, publically available dataset.
Materials and Methods : 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 effects meta-analysis model was used to generate a pooled estimate for all cohorts.
Results : The classifier was associated with prognosis in ten of the twelve cohorts (p<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 (Hazard Ratio [HR], 2.66; 95% Confidence Interval [CI], 1.93-3.67; P<0.0001) patients and in stratified analyses of stage IA (HR, 2.69; 95%CI, 1.66-4.35; P<0.0001) and stage IB (HR, 2.69; 95%CI, 1.74-4.16; P<0.0001) patients.
Conclusions : The -4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors
Impact: Our results suggest that the 4-gene classifier may assist clinicians in decisions regarding postoperative management of early stage lung adenocarcinoma patients.
Cancer Epidemiology Biomarkers & Prevention , résumé, 2014