CircZNF609 as a potential prognostic biomarker across multiple cancers: a systematic review and meta-analysis with ceRNA network exploration.

BACKGROUND: CircZNF609 (hsa_circ_0000615), a back-spliced transcript derived from the ZNF609 gene locus, has garnered increasing attention for its functional roles in tumor progression across multiple cancer types. However, no pan-cancer meta-analysis has systematically evaluated its prognostic value and association with clinicopathological aggressiveness. We therefore performed this systematic review and meta-analysis to synthesize all available clinical evidence addressing this critical gap. METHODS: We systematically retrieved literature from five databases (PubMed, Web of Science, Embase, the Cochrane Library and CNKI) up to April 2, 2026. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were synthesized to quantify the link between circZNF609 levels and overall survival (OS) or clinicopathological variables. Heterogeneity assessment, sensitivity analysis, and publication bias evaluation were also performed. Additionally, a circZNF609-mediated ceRNA network was reconstructed based on experimentally validated targets. RESULTS: A total of 12 studies involving 791 patients were included in this meta-analysis. Elevated circZNF609 expression was significantly associated with worse overall survival (HR = 2.31, 95% CI:1.74-3.07, P < 0.001; I² = 55.2%). Additionally, high circZNF609 expression was correlated with advanced TNM stage (OR = 2.34, 95% CI: 1.68-3.27, P < 0.001) and increased risk of lymph node metastasis (OR = 5.28, 95% CI: 3.48-8.00, P < 0.001). No significant associations were found between circZNF609 expression and age, sex, tumor size, or histological differentiation. Sensitivity analyses confirmed the robustness of the pooled results, and Begg's test (P = 0.493) and Egger's regression test (P = 0.197) indicated no significant publication bias. Mechanistically, the reconstructed ceRNA network suggested that circZNF609 may exert oncogenic effects via cell-cycle and metastasis-related pathways. CONCLUSIONS: Increased circZNF609 expression is associated with adverse survival outcomes and aggressive clinicopathological behavior across multiple malignancies. The ceRNA network offers mechanistic support for these clinical associations. CircZNF609 warrants validation in prospective, multi-ethnic cohorts as a promising prognostic biomarker and candidate therapeutic target.