Tumor-derived exosomal miR-155-5p and miR-658 in serum as diagnostic biomarkers for early-stage non-small cell lung cancer

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background Exosomal microRNAs (ExmiRNAs) provided a non-invasive and ideal method for cancer diagnosis. However, few studies identified the role of specific serum ExmiRNAs profiles in early non-small cell lung cancer (NSCLC) diagnosis, especially for 0 and I stage. Herein, the present study was designed to validate the novel serum ExmiRNAs as diagnostic biomarkers for early-stage NSCLC. Methods Serum exosomes were collected from the healthy donors and NSCLC patients by ultracentrifugation, and characterized with qNano, TEM, and western immunoblotting. Exosomal RNAs were subjected to miRNA array for evaluating the expression levels of miRNAs. Partly differently expressed serum exosomal miRNAs were verified by large-scale samples from 312 healthy donors and 318 NSCLC patients. Results The expression levels of ExmiR-155-5p and ExmiR-658 were significantly down-regulated in NSCLC patients compared to healthy donors (<jats:italic>p</jats:italic> &lt; 0.0001 and <jats:italic>p</jats:italic> &lt; 0.0001, respectively), and they could differentiate NSCLC patients from healthy donors with area under the ROC curve (AUC) of 0.716 and 0.728, respectively. In addition, combination of ExmiR-155-5p and ExmiR-658 could improve the diagnostic capacity with AUC value of 0.781. Moreover, ExmiR-155-5p and ExmiR-658 could differentiate early-stage NSCLC patients (0 and I stage) from healthy donors with AUC values of 0.668 and 0.735, respectively, combination could improve the diagnostic capacity with AUC value of 0.759. Specifically, the expression of ExmiR-155-5p was significantly decreased in patients with lymph node metastasis and distant metastasis (<jats:italic>p</jats:italic> = 0.0018 and <jats:italic>p</jats:italic> = 0.0077, respectively). Conclusions Our results identified that serum ExmiR-155-5p and ExmiR-658 were promising diagnostic biomarkers for early-stage NSCLC, and combination of them could improve the diagnostic capacity.</jats:p>