Circular RNAs Serve as Prognostic, Diagnostic and Clinicopathological Markers in Lung Cancer: An Updated Systematic Review and Meta-Analysis

Abstract Background: In recent years, the roles of circular RNAs (circRNAs) in the biogenesis and clinical application have gradually garnered much interest in the field of cancer research. However, high-quality studies evaluating the roles of circRNAs in clinicopathological features and clinical application of lung cancer are still unrevealed. Herein, we aimed to elucidate the functions of circRNAs in the association with clinicopathology, diagnosis and prognosis in lung cancer. Methods: Comprehensive and reasonable search strategies were used in four databases up to Nov. 24th, 2019. The odds ratio (OR) was used to analyze the risks of circRNAs in lung cancer. Sensitivity (Sen), specificity (Spe) and area under curve (AUC) were used to assess the diagnostic value. What’s more, the hazard ratio (HR) was used for the analysis of survival outcomes. A fixed-effect model was firstly used in data analysis. If I2 >50% in heterogeneity, the random-effect model was chosen. Results: A total of 50 studies with 3815 samples were incorporated into our meta-analysis, in which 40 focused on clinical characteristics, 10 related to diagnosis and 31 were aimed at prognosis. In terms of clinical characteristics, both OR and 95% confidence interval (95%CI) were shown that circRNAs were significantly associated with TNM, tumor differentiation, lymph node metastasis, distal metastasis and tumor size in lung cancer. For diagnosis, both upregulated and downregulated circRNAs distinguished patients with lung cancer from healthy people with pooled Sen, Spe and AUC, of which the values were 0.78, 0.76 and 0.81 respectively. In the section of prognosis, circRNAs can better predict the survival time of patients with lung cancer (overall survival, OS: HR=0.46, 95%Cl: 0.33–0.65 in downregulated circRNAs; HR=2.23, 95%CI: 1.97-2.53 in upregulated circRNAs). Conclusions: The results presented here suggested that circRNAs were the potential cancer biomarkers in clinicopathology, diagnosis and prognosis of lung cancer patients, which deserve further application in clinical practice.