@article {198, title = {A 12-gene set predicts survival benefits from adjuvant chemotherapy in non-small cell lung cancer patients.}, journal = {Clin Cancer Res}, volume = {19}, year = {2013}, month = {2013 Mar 15}, pages = {1577-86}, abstract = {

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.

}, keywords = {Adult, Aged, Carcinoma, Non-Small-Cell Lung, Chemotherapy, Adjuvant, Clinical Trials as Topic, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Male, Middle Aged, Neoplasm Proteins, Neoplasm Staging, Prognosis, RNA Interference, Systems Biology, Treatment Outcome}, issn = {1078-0432}, doi = {10.1158/1078-0432.CCR-12-2321}, author = {Tang, Hao and Xiao, Guanghua and Behrens, Carmen and Schiller, Joan and Allen, Jeffrey and Chow, Chi-Wan and Suraokar, Milind and Corvalan, Alejandro and Jiang-Hua Mao and White, Michael A and Wistuba, Ignacio I and Minna, John D and Xie, Yang} }