Accumulating evidence has demonstrated that
circular RNAs (
circRNAs) play vital roles in
cancer progression. However, the underlying molecular mechanisms of
circRNAs remain poorly elucidated in
gastric cancer (GC). The main purpose of present study is to explore the underlying regulatory mechanism by constructing a
circRNA-associated
competitive endogenous RNA (
ceRNA) network and further establish a robust prognostic signature for patients with GC. Based on expression data of
circRNA,
microRNA, and
mRNA derived from Gene Expression Omnibus (GEO) and The
Cancer Genome Atlas (TCGA) databases, a
circRNA-associated
ceRNA network, containing 15 cirRNAs, 9
microRNAs, and 35 mRNAs, was constructed using the Starbase database. Functional enrichment analysis showed that the
ceRNA network might be involved in many
cancer-related pathways, such as regulation of transcription from
RNA polymerase II promoter, mesodermal cell differentiation, and focal adhesion. A protein-protein interaction network was constructed based on genes within the
circRNA-associated
ceRNA network. We found that six of ten hub genes within the PPI network were significantly associated with overall survival (OS). Thus, using the LASSO method, we constructed a three-gene prognostic signature based on TCGA-GC cohort, which could classify GC patients into low-risk and high-risk groups with significant difference in OS (HR = 1.9, 95%CI = 1.14-3.2, and log-rank p = 0.001). The prognostic performance of the three-gene signature was verified in GSE15459 (HR = 1.9, 95%CI = 1.27-3.0, and log - rank p = 2.2E - 05) and GSE84437 (HR = 1.5, 95%CI = 1.17-2.0, and log - rank p = 6.3E - 04). Multivariate Cox analysis further revealed that the three-gene prognostic signature could serve as an independent risk factor for OS. Taken together, our findings contribute to a better understanding of the underlying mechanisms of
circRNAs in GC progression. Furthermore, a robust prognostic signature is meaningful to facilitate individualized treatment for patients with GC.