CircRNA CeRNA networks in gastric cancer highlight FAP/FNDC1 as potential prognostic and therapeutic targets

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).

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.

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.

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.