A Three-Gene Prognostic Signature Based on Circular RNA-Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma
Abstract Background: Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, functions of circRNAs in lung adenocarcinoma (LUAD) are still unknown. It is necessary to investigate the regulatory mechanism of circRNAs based on competing endogenous RNA (ceRNA) network in LUAD procession and further construct a prognostic signature for predicting overall survival of LUAD patients.Methods: Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network based on TargetScan prediction tool and Pearson correlation coefficient. Functional and pathway enrichment analysis were performed using DAVID database. A PPI network was constructed and then visualized by Cytoscape software. Finally, we constructed a prognostic signature for LUAD patients using LASSO method and assessed the prognostic performance in the validation cohort.Results: A total of 38 DEcircRNAs, 56 DEmiRNAs, and 960 DEmRNAs were identifed. Based on the interactions predicted by TargetScan, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs and 49 DEmRNAs. GO and KEGG pathway analysis indicated that the circRNA-associated ceRNA network might be involved in regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using LASSO method. By applying the signature, patients in the training cohort could be categorized into high-risk or low-risk subgroup with significant survival difference (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent GEO cohort (HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Multivariate cox regression analysis proved that the three-gene signature was an independent prognostic factor for LUAD.Conclusions: Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and constructed a prognostic signature that could be a useful guide for personalized treatment of LUAD patients.