Identification of three circular RNA cargoes in serum exosomes as diagnostic biomarkers of non-small-cell lung cancer in the Chinese population.

The recent discovery of circular RNAs (circRNAs) in serum exosomes has suggested a novel and potentially useful tool for cancer non-invasive diagnosis. However, there is yet, no substantial studies addressing this topic. RNA-seq analysis was performed between three pairs of non-small-cell lung cancer (NSCLC) patients and controls. The diagnostic values of exosomal circRNAs were assessed in a training set, validation set 1 and validation set 2. A total of 46 abnormally expressional circRNAs were identified. Among these, circ_0047921, circ_0056285 and circ_0007761 were found to display significantly diagnostic validity of NSCLC. In distinguishing NSCLC cases from healthy controls, the panel of aforementioned circRNAs exhibited area under curve (AUC) values of 0.926 (95% confidence interval[CI] = 0.895-0.956) in training set and 0.919 (95%CI = 0.877-0.962) in validation set 1. Circ_0047921 could distinguish NSCLC cases from COPD controls (AUC = 0.890, 95%CI = 0.831-0.948), while the circ_0056285 and circ_0007761 combination could distinguish NSCLC cases from tuberculosis controls (AUC = 0.820, 95%CI = 0.739-0.902). For an early NSCLC diagnosis, similar results were observed for these circRNAs in distinguishing early-stage NSCLC cases from healthy controls, COPD controls or TB controls. Circ_0056285 expression was correlated with clinical stages and lymph node metastasis. The exosomal circRNAs, circ_0047921, circ_0056285 and circ_0007761 are promising biomarkers for NSCLC diagnosis in the Chinese population.