A 12-gene set predicts survival benefits from adjuvant chemotherapy in non-small cell lung cancer patients

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

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134 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1577-1586
Number of pages10
JournalClinical Cancer Research
Volume19
Issue number6
DOIs
StatePublished - Mar 15 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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