Five-Gene Signature for Survival in Non–Small-Cell Lung Cancer Patients

Summary and Comment |
January 29, 2007

Five-Gene Signature for Survival in Non–Small-Cell Lung Cancer Patients

  1. Stephen G. Swisher, MD, and Henry Mark Kuerer, MD, PhD, FACS

Expression patterns of five genes predict relapse-free and overall survival in resected NSCLC patients.

  1. Stephen G. Swisher, MD, and Henry Mark Kuerer, MD, PhD, FACS

Non–small-cell lung cancer (NSCLC) is the most common cause of cancer death in the U.S. Long-term survival depends largely on the pathologic stage of the tumor, which can be assessed with the AJCC pTNM staging system. Yet, even in patients with early-stage NSCLC, the relapse rate is as high as 40% after curative surgical resection. The current staging system for lung cancer cannot predict which patients are likely to experience recurrences, so identifying patients who will benefit most from adjuvant chemotherapy is difficult.

To determine whether genetic signatures could be used to predict relapse-free and overall survival within current staging groups, researchers from Taiwan evaluated specimens from 125 NSCLC patients who underwent resection at the Taichung Veterans General Hospital from 2000 to 2003. Specimens were randomly assigned to reverse-transcriptase (RT)-PCR, microarray analysis, or both. Risk scores and decision-tree analysis were used to develop a gene-expression model for predicting relapse and overall survival. Expression of 16 genes correlated with survival initially; a refined model included 5 of these genes (DUSP6, MMD, STAT1, ERBB3, and LCK). This five-gene RT-PCR signature was validated in an independent group of 60 additional NSCLC specimens. Furthermore, published microarray data from 86 patients with known outcomes corroborated the prognostic validity of these five genes.

Comment

The identification of a five-gene signature that reliably predicts relapse in NSCLC patients might allow selection of high-risk patients for adjuvant chemotherapy. Additionally, the products of these five genes might be targets for development of molecular-based therapeutics. However, the results of this preliminary study must be confirmed by prospective studies to determine whether these techniques are reproducible and can be employed reliably in other settings.

Dr. Swisher is a Professor of Thoracic and Cardiovascular Surgery at the University of Texas M.D. Anderson Cancer Center in Houston, Texas.

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