Abstract B35: The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts.

Abstract

Abstract We previously developed and validated a prognostic classifier using the mRNA expression levels of BRCA1, HIF1A, DLC1, and XPO1. This 4-gene classifier aimed to identify stage I lung adenocarcinoma patients with a high risk of relapse. Our initial study evaluated patients in five independent cohorts from various regions of the world, suggesting that the 4-gene classifier was robust and representative of most lung adenocarcinomas. In an attempt to further validate this classifier, we have used a meta-analysis based approach to study 12 cohorts consisting of 1069 TNM stage I lung adenocarcinoma patients. These cohorts were obtained through a systematic search of public gene expression datasets and all suitable datasets were analyzed. Kaplan-Meier analysis of each cohort showed that the classifier was significantly associated with prognosis in ten of the twelve cohorts (p<0.05). The association was highly consistent across all cohorts regardless of the ethnic diversity or microarray platform and there was no evidence of heterogeneity across all cohorts (I2 = 0.0%, p=0.98). 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. These results suggest that the 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors and may assist clinicians in decisions regarding postoperative management of early stage patients. Citation Format: Hirokazu Okayama, Aaron J. Schetter, Teruhide Ishigame, Ana I. Robles, Takashi Kohno, Jun Yokota, Seiichi Takenoshita, Curtis C. Harris. The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B35.