Abstract
OBJECTIVE: Circular RNAs (circRNAs) are endogenous non-coding RNAs implicated in the initiation and progression of cancer. The circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network exerts a crucial influence on tumor prognosis and therapy. This research aimed to identify novel circRNA-driven ceRNA networks and potential prognostic/therapeutic targets for gastric cancer (GC). METHODS: Gastric cancer-related circRNA, miRNA, and mRNA datasets were retrieved from the GEO database, accompanied by clinical and expression data from TCGA. Differential expression analysis, ceRNA network construction (Cytoscape_v3.8.0), KEGG/GO enrichment analysis, and survival analyses were conducted using R software. RESULTS: KEGG analysis of mRNAs within the ceRNA network indicated enrichment in the IL-17 signaling pathway, TNF signaling pathway, and other pathways associated with GC prognosis. Two key ceRNA axes associated with GC prognosis were identified: (1) hsa_circ_0055521/hsa-miR-204-5p/FAP and (2) (hsa_circ_0005051, hsa_circ_0007613, hsa_circ_0045602, hsa_circ_0034398, hsa_circ_0006089)/hsa-miR-32-3p/FNDC1. Survival analysis and immunohistochemical validation (HPA database) verified that FAP and FNDC1 are potential prognostic biomarkers and therapeutic targets for GC. CONCLUSION: This study identifies three key pathways, two novel prognostic ceRNA networks, six prognosis-related circRNAs, and two target genes (FAP/FNDC1) for GC, offering new directions for GC therapy.