Alterations in bronchial airway microRNA expression for lung cancer detection

We have previously shown that gene-expression alterations in cytologically normal appearing bronchial epithelial cells can be used as a biomarker for lung cancer detection in smokers (Whitney et al., BMC Medical Genomics 2015; Silvestri et al., NEJM 2015). In this study, we have established that there are also alterations in bronchial microRNA-expression of smokers with lung cancer. Importantly, the performance of an existing bronchial mRNA-biomarker has been improved by integrating microRNA with mRNA expression. Using bronchial brushings collected from current and former smokers undergoing bronchoscopy for suspected lung cancer as part of the AEGIS-1/2 clinical trials, we profiled microRNA-expression via small-RNA sequencing in samples from 347 patients for which gene-expression data was also available. Patients were followed prospectively for up to one year until a final diagnosis of cancer (n=194) or benign disease (n=153) was made. After filtering-out 6 low-quality sequencing samples, we assigned 138 patients (AEGIS-1) to be used as a discovery set and the remaining 203 samples (AEGIS-1/2) were used as an independent test set.