A Gene Expression Signature to Predict Metastasis and Survival in Non-small Cell Lung Cancer

Background: Current histopathological methods are inadequate for predicting outcome and recurrence in patients with non-small cell lung carcinoma (NSCLC) after surgery. In this study, we investigated the use of gene expression signatures to predict outcome and metastasis in lung cancer patients. Methods: Gene expression was studied by microarray and the real-time reverse transcriptase polymerase chain reaction (RT-PCR) in normal and lung tumor tissue of 188 NSCLC patients who underwent surgical resection. The 5 cancer-related genes and 1 reference gene expression levels measureed by real-time RT-PCR were used in a prospectively defined algorithm to determine the risk for each patient. Finally, we used an independent cohort to verify the 5 gene-based predictive model derived from decision tree analysis. Results: The 5 gene-based decision tree model was able to predict the prognosis. The recurrence rate at 36 months was 53% in the low-risk group versus 83% in the high-risk group (P=0.002). The 5 gene-based model could also predict overall survival (P<0.001). In multivariate analysis, the decision tree model predicted that high-low dichotomy and stage were both significant for recurrence. In addition, it could also predict metastasis and survival of NSCLC patients within the stage I-II subgroups. A similar result was found using an independent cohort of NSCLC patients. The high-risk patients had a significantly poorer overall survival than the low-risk patients (P=0.005). We also found distinct gene signatures which could distinguish between NSCLC, and normal tissue and histology subtypes. Conclusions: A gene expression signature can predict metastasis and survival of NSCLC patients. Keywords: Survival and metastasis analysis In this study, we investigated the use of gene expression signatures to predict outcome and metastasis in lung cancer patients. Lung cancer tissue specimens from 125 patients who underwent surgical resection of their primary NSCLC at the Taichung Veterans General Hospital in Taiwan between December 1999 and December 2003 were included in this study. Specimens were stored frozen. Of these patients, 60 had adenocarcinoma, 52 squamous cell carcinoma, and 13 other types, all histologically defined.