Clinicopathological and prognostic significance of circRNAs in lung cancer A systematic review and meta-analysis

Background: Circular RNAs (circRNAs) regulate multiple pathways during lung cancer pathogenesis. Apart from functional significance, many circRNAs have been shown to be associated with clinicopathological characteristics and predict lung cancer prognosis. Our aim is to summarize the expanding knowledge of clinical roles of circRNAs in lung cancer. Methods: A thorough search of literature was conducted to identify articles about the correlation between circRNA expression and its prognostic and clinicopathological values. Biological mechanisms were summarized. Results: This study included 35 original articles and 32 circRNAs with prognostic roles for lung cancer. Increased expression of 25 circRNAs and decreased expression of 7 circRNAs predicted poor prognosis. For non-small cell lung cancer, changes of circRNAs were correlated with tumor size, lymph node metastasis, distant metastasis, tumor node metastasis (TNM) stage, and differentiation, indicating the major function of circRNAs is to promote lung cancer invasion and migration. Particularly, meta-analysis of ciRS-7, hsa_circ_0020123, hsa_circ_0067934 showed increase of the 3 circRNAs was associated with positive lymph node metastasis. Increase of ciRS-7 and hsa_circ_0067934 was also related with advanced TNM stage. The biological effects depend on the general function of circRNA as microRNA sponge. Conclusions: CircRNAs have the potential to function as prognostic markers and are associated with lung cancer progression and metastasis.