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

Dan J. Raz, M. Roshni Ray, Jaey Y. Kim, Biao He, Miquel Taron, Marcin Skrzypski, Mark Segal, David R Gandara, Rafael Rosell, David M. Jablons

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62 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5565-5570
Number of pages6
JournalClinical Cancer Research
Volume14
Issue number17
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Raz, D. J., Ray, M. R., Kim, J. Y., He, B., Taron, M., Skrzypski, M., Segal, M., Gandara, D. R., Rosell, R., & Jablons, D. M. (2008). A multigene assay is prognostic of survival in patients with early-stage lung adenocarcinoma. Clinical Cancer Research, 14(17), 5565-5570. https://doi.org/10.1158/1078-0432.CCR-08-0544