Circulating Neutrophil MicroRNAs as Biomarkers for the Detection of Lung Cancer

Abstract

Peripheral neutrophils are the predominant circulating leukocytes and an important component of innate and adaptive immune systems, which is a primary defense against cancer. MicroRNAs (miRNAs) can modulate neutrophil functions and play important roles in cancer pathogenesis by regulating neutrophil gene expression. To investigate if assessment of differential miRNA levels of peripheral neutrophils has the potential for diagnosis of non-small-cell lung cancer (NSCLC), we examine neutrophils of 15 patients with stage I NSCLC and 15 smokers without cancer. We identify five neutrophil miRNAs that have an abnormal level in patients with NSCLC versus smokers without cancer. In a training set of 82 patients with lung cancer and 73 controls, a set of two genes (miRs-26a-2-3p and 574-3p) are developed, producing 77.8% sensitivity and 78.1% specificity for NSCLC detection. Furthermore, in a testing set of 60 patients with lung cancer and 58 smokers, the performance of analyzing the two miRNAs for lung cancer detection is confirmed. This study for the first time shows that a neutrophil miRNA profile may serve as a new category of circulating biomarkers for the detection of NSCLC.

Keywords: biomarkers; diagnosis; lung cancer; microRNA; peripheral neutrophils.

Figure 1

Expression levels of two miRNAs in neutrophil samples of 82 cancer-free smokers and 73 patients with NSCLC. The two miRNAs (A and B) have statistically significantly different levels in the patients with NSCLC versus cancer-free smokers (all P < 0.05). The inside line denotes the median.

Figure 2

ROC curve analysis of expression levels of two miRNAs (miRs-26a-2-3p and -574-3p) in neutrophils of 82 patients diagnosed with NSCLC and 73 cancer-free individuals. miRs-26a-2-3p and -574-3p produce 0.71–0.74 AUC values (A and B), being significantly lower than 0.81 AUC created from the combined use of the two miRNAs (C) (P < 0.05).