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A Multigene Assay Is Prognostic of Survival in Patients with Early-Stage Lung Adenocarcinoma

Authors' Affiliations: ¹ Thoracic Oncology Program, Department of Surgery and ² Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California; ³ Catalan Institute of Oncology, Hospital Germans Trias I Pujol, Barcelona, Spain; ⁴ Medical University of Gdansk, Gdansk, Poland; and ⁵ Divison of Hematology/Oncology, University of California Davis Cancer Center, Sacramento, California

Requests for reprints: Dan J. Raz, University of California, San Francisco, 513 Parnassus Avenue S-321, San Francisco, CA 94131. Phone: 415-476-1239; Fax: 415-353-9530; E-mail: Dan.raz{at}ucsf.edu.

Purpose: Clinical staging does not adequately risk stratify patients with early stage non–small cell lung cancer. We sought to generate a real-time PCR (RT-PCR)–based prognostic model in patients with early stage lung adenocarcinoma, the dominant histology of lung cancer in the United States.

Experimental Design: We studied gene expression of 61 candidate genes in 107 patients with completely surgically resected lung adenocarcinoma using RT-PCR. We used crossvalidation methods to select and validate a prognostic model based on the expression of a limited number of genes. A risk score was generated based on model coefficients, and survival of patients with high- and low-risk scores were analyzed.

Results: We generated a four-gene model based on expression of WNT3a, ERBB3, LCK, and RND3. Risk score predicted mortality better than clinical stage or tumor size (adjusted hazard ratio, 6.7; 95% confidence interval, 1.6-28.9; P = 0.001). Among 70 patients with stage I disease, 5-year overall survival was 87% among patients with low-risk scores, and 38% among patients with high-risk scores (P = 0.0002). Among all patients, 5-year overall survival was 62% and 41%, respectively (P = 0.0054). Disease-free survival was also significantly different among low- and high-risk score patients.

Conclusions: This multigene assay predicts overall and disease-free survival significantly better than clinical stage and tumor size in patients with early stage lung adenocarcinoma and performs especially well in patients with stage I disease. Prospective clinical trials are needed to determine whether high-risk patients with stage I disease benefit from adjuvant chemotherapy.