Circulating circTOLLIP serves as a diagnostic biomarker for liquid biopsy in non-small cell lung cancer

Background: Circular RNAs (CircRNAs) have been found to possess vital functions in tumorigenesis of various cancer types, including non-small cell lung cancer (NSCLC). The aim of this study was to identify and explore the diagnostic values of the newly found Toll interacting protein (TOLLIP)-derived circRNA (circTOLLIP) for liquid biopsy in NSCLC. Methods: RNase R and actinomycin D assays were conducted to confirm the existence and stability of circTOLLIP. RT-qPCR was performed to identify the expression levels of circTOLLIP in NSCLC tumor tissues, whole blood, and cell lines. The diagnostic values were evaluated by receiver operating characteristic (ROC) curve analysis. Results: CircTOLLIP was screened as a candidate biomarker and was found to be significantly down-regulated in both NSCLC tissues and cell lines. Interestingly, circulating circTOLLIP was also lower-expressed in the whole blood of patients with NSCLC compared to that of patients with benign lung disease and healthy controls. Importantly, the circulating circTOLLIP represented better diagnostic values in comparison to the traditional tumor markers (NSE, CYFR21-1, and CA72-4), and showed higher stability even though the whole blood was exposed to various tough conditions. Conclusions: Our findings indicate that circTOLLIP can be used as a non-invasive biomarker to distinguish earlystage NSCLC from benign lung diseases and from healthy controls, suggesting the potential application of circTOLLIP for liquid biopsy in NSCLC.