Abstract
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide. Among various histological types of lung cancer, majority are non-small cell lung cancer (NSCLC) which account for > 80%. Circular RNAs (circRNAs) are widely expressed in various cancers including lung cancer and implicated in tumourigenesis and cancer progression. This study aimed to systematically evaluate the prognostic values of circRNAs in lung cancer. METHODS: A systematic literature search was done in PubMed, Embase, and MEDLINE databases to select the eligible studies which reported the association between the expression of circRNAs and overall survival (OS) or disease-free survival (DFS) in histopathologically diagnosed lung cancer patients. The pooled hazard ratio (HR) and 95% confidence interval (CI) were assessed to determine the prognostic significance of circRNAs. RESULTS: A total of 43 studies were eligible for this meta-analysis (MA). 39 different types of circRNAs were reported: 28 showing upregulating and 11 showing downregulating action in lung cancer. High expression of circRNAs with upregulating action in lung cancer was associated with worse prognosis and poor OS (HR 1.93, 95% CI [1.61-2.33], p < 0.00001). High expression of circRNAs with downregulating action in lung cancer was associated with favorable OS and prognosis (HR 0.73, 95% CI [0.58-0.94], p = 0.01). However, there was no statistically significant association between high and low expression of both upregulating and downregulating circRNAs and DFS (HR 1.44, 95% CI [0.92-2.24], p = 0.11). CONCLUSIONS: This MA confirmed the pivotal role of circRNAs as important prognostic biomarkers for lung cancer, especially NSCLC. High expression of upregulating circRNAs is associated with poor prognosis; however, high expression of downregulating circRNAs is associated with favorable prognosis. Therefore, downregulatory action of circRNAs should be considered a promising treatment in the management of lung cancer, especially NSCLC.