A 12-Gene Set Predicts Survival Benefits from Adjuvant Chemotherapy in Non-Small Cell Lung Cancer Patients

作者：Tang Hao; Xiao Guanghua; Behrens Carmen; Schiller Joan; Allen Jeffrey; Chow Chi Wan; Suraokar Milind; Corvalan Alejandro; Mao Jianhua; White Michael A; Wistuba Ignacio I; Minna John D; Xie Yang^*

来源：Clinical Cancer Research, 2013, 19(6): 1577-1586.

DOI：10.1158/1078-0432.CCR-12-2321

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. %26lt;br%26gt;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. %26lt;br%26gt;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). %26lt;br%26gt;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. Clin Cancer Res; 19(6); 1577-86.

• 出版日期2013-3-15