%0 Journal Article %J Clin Cancer Res %D 2013 %T A 12-gene set predicts survival benefits from adjuvant chemotherapy in non-small cell lung cancer patients. %A Tang, Hao %A Xiao, Guanghua %A Behrens, Carmen %A Schiller, Joan %A Allen, Jeffrey %A Chow, Chi-Wan %A Suraokar, Milind %A Corvalan, Alejandro %A Jiang-Hua Mao %A White, Michael A %A Wistuba, Ignacio I %A Minna, John D %A Xie, Yang %K Adult %K Aged %K Carcinoma, Non-Small-Cell Lung %K Chemotherapy, Adjuvant %K Clinical Trials as Topic %K Female %K Gene Expression Regulation, Neoplastic %K Genome, Human %K Humans %K Kaplan-Meier Estimate %K Lung Neoplasms %K Male %K Middle Aged %K Neoplasm Proteins %K Neoplasm Staging %K Prognosis %K RNA Interference %K Systems Biology %K Treatment Outcome %X

PURPOSE: Prospectively identifying who will benefit from adjuvant chemotherapy (ACT) would improve clinical decisions for non-small cell lung cancer (NSCLC) patients. In this study, we aim to develop and validate a functional gene set that predicts the clinical benefits of ACT in NSCLC.

EXPERIMENTAL DESIGN: An 18-hub-gene prognosis signature was developed through a systems biology approach, and its prognostic value was evaluated in six independent cohorts. The 18-hub-gene set was then integrated with genome-wide functional (RNAi) data and genetic aberration data to derive a 12-gene predictive signature for ACT benefits in NSCLC.

RESULTS: Using a cohort of 442 stage I to III NSCLC patients who underwent surgical resection, we identified an 18-hub-gene set that robustly predicted the prognosis of patients with adenocarcinoma in all validation datasets across four microarray platforms. The hub genes, identified through a purely data-driven approach, have significant biological implications in tumor pathogenesis, including NKX2-1, Aurora Kinase A, PRC1, CDKN3, MBIP, and RRM2. The 12-gene predictive signature was successfully validated in two independent datasets (n = 90 and 176). The predicted benefit group showed significant improvement in survival after ACT (UT Lung SPORE data: HR = 0.34, P = 0.017; JBR.10 clinical trial data: HR = 0.36, P = 0.038), whereas the predicted nonbenefit group showed no survival benefit for 2 datasets (HR = 0.80, P = 0.70; HR = 0.91, P = 0.82).

CONCLUSIONS: This is the first study to integrate genetic aberration, genome-wide RNAi data, and mRNA expression data to identify a functional gene set that predicts which resectable patients with non-small cell lung cancer will have a survival benefit with ACT.

%B Clin Cancer Res %V 19 %P 1577-86 %8 2013 Mar 15 %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/23357979?dopt=Abstract %R 10.1158/1078-0432.CCR-12-2321