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Clin Cancer Res. 2008 Sep 1;14(17):5565-70. doi: 10.1158/1078-0432.CCR-08-0544.

A multigene assay is prognostic of survival in patients with early-stage lung adenocarcinoma.

Author information

  • 1Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, California 94131, USA. Dan.raz@ucsf.edu

Abstract

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.

PMID:
18765549
[PubMed - indexed for MEDLINE]
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