Peripheral Blood-derived CircVPS35L as a Potential Diagnostic Biomarker for Non-small Cell Lung Cancer

Introduction: Circular RNAs (circRNAs) are dysregulated in cancers and are stably expressed in body fluids such as blood. We therefore identified and evaluated the clinical value of a newly found circRNA VPS35L (circVPS35L) as a biomarker for the diagnosis of non-small cell lung cancer (NSCLC). Methods: Reverse-transcription quantitative PCR (RT-qPCR) was used to determine the expression levels of circVPS35L in tissues, whole blood, and cell lines. The actinomycin D assay and RNase R treatment were utilized to determine the stability of circVPS35L. Receiver operating characteristic (ROC) curve analysis was conducted to predict the diagnostic value of blood-derived circVPS35L in NSCLC. Results: CircVPS35L was found to be downregulated in NSCLC tissues and cell lines. Interestingly, circVPS35L expression was significantly correlated with tumor size (P = 0.0269), histology type (P < 0.0001), and TNM stage (P = 0.0437). Importantly, circVPS35L was poorly expressed in peripheral blood of NSCLC patients when compared with healthy controls and patients with benign lung disease. ROC analysis revealed a higher diagnostic value of circVPS35L than the three conventional tumor markers (CYFR21-1, NSE, and CEA) in patients with NSCLC. Moreover, circVPS35L was highly stable in peripheral blood when exposed to undesirable conditions. Conclusion: These findings demonstrate that circVPS35L has great potential as a novel biomarker for the diagnosis of NSCLC, and can be used to distinguish NSCLC from benign lung disease.

Automated summary

Circular RNAs (circRNAs) are dysregulated in cancers and have stable expression in body fluids. This study identified and evaluated the clinical value of circRNA VPS35L (circVPS35L) as a biomarker for diagnosing non-small cell lung cancer (NSCLC). The expression levels of circVPS35L were determined in tissues, blood, and cell lines using RT-qPCR. The stability of circVPS35L was examined with the actinomycin D assay and RNase R treatment. ROC analysis showed that circVPS35L had higher diagnostic value than conventional tumor markers in NSCLC patients. Furthermore, circVPS35L was highly stable in peripheral blood. These findings highlight the potential of circVPS35L as a novel biomarker for NSCLC diagnosis and differentiation from benign lung disease.