Molecular gene signature and prognosis of non-small cell lung cancer

Abstract

The current staging system for non-small cell lung cancer (NSCLC) is inadequate for predicting outcome. Risk score, a linear combination of the values for the expression of each gene multiplied by a weighting value which was estimated from univariate Cox proportional hazard regression, can be useful. The aim of this study is to analyze survival-related genes with TaqMan Low-Density Array (TLDA) and risk score to explore gene-signature in lung cancer. A total of 96 NSCLC specimens were collected and randomly assigned to a training (n = 48) or a testing cohort (n = 48). A panel of 219 survival-associated genes from published studies were used to develop a 6-gene risk score. The risk score was used to classify patients into high or low-risk signature and survival analysis was performed. Cox models were used to evaluate independent prognostic factors. A 6-gene signature including ABCC4, ADRBK2, KLHL23, PDS5A, UHRF1 and ZNF551 was identified. The risk score in both training (HR = 3.14, 95% CI: 1.14-8.67, p = 0.03) and testing cohorts (HR = 5.42, 95% CI: 1.56-18.84, p = 0.01) was the independent prognostic factor. In merged public datasets including GSE50081, GSE30219, GSE31210, GSE19188, GSE37745, GSE3141 and GSE31908, the risk score (HR = 1.50, 95% CI: 1.25-1.80, p < 0.0001) was also the independent prognostic factor. The risk score generated from expression of a small number of genes did perform well in predicting overall survival and may be useful in routine clinical practice.