Integrative In Silico Multi-Omics Profiling of circRNA-Mediated ceRNA Networks Reveals Prognostic Biomarkers and Repurposed Therapeutic Candidates in Gastric Cancer.

Gastric cancer (GC), also known as stomach adenocarcinoma (STAD), remains a highly lethal malignancy due to late diagnosis, limited therapeutic efficacy, and frequent metastasis. Although extensive molecular profiling has been performed, post-transcriptional regulatory mechanisms underlying GC progression are still incompletely characterized. In this study, we applied an integrative multi-omics framework to elucidate the regulatory roles and clinical relevance of circular RNAs (circRNAs) in GC. Transcriptomic data of mRNAs, microRNAs, and circRNAs from eight independent GEO datasets were jointly analyzed, resulting in the identification of 249 differentially expressed genes (DEGs), 8 differentially expressed microRNAs (DEmiRNAs), and 4 differentially expressed circRNAs (DEcircRNAs). These molecules were integrated into a competing endogenous RNA (ceRNA) network, enabling systems-level characterization of GC-associated regulatory interactions. Network topology and survival analyses prioritized 13 hub molecules, including IGF2BP3, COL4A1, MMP14, and TGM2, which showed both central network positions and significant associations with patient survival. To explore therapeutic implications, transcriptomics-guided drug repositioning combined with molecular docking analysis identified five candidate compounds-celastrol, fedratinib, pevonedistat, tozasertib, and withaferin A-predicted to target key network hubs. Overall, this in silico study provides a ceRNA-centered regulatory framework for GC and prioritizes biologically informed biomarkers and repositioned drug candidates with potential applicability across other malignancies to converge precision oncology.