Prognostic Value of Circular RNAs in Digestive System Malignancies: Evidence From a Systematic Review and Meta-analysis

Dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of various cancers.However, their clinicopathological and prognostic value in digestive system malignancies remains unclear.This metaanalysis was performed to investigate the potential prognostic role of circRNAs in these cancers, classifying them as oncogenic or tumor-suppressor based on original study findings, while noting context-dependent roles.A comprehensive electronic literature search was conducted to identify eligible studies evaluating the prognostic significance of circRNAs in digestive cancers.Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated to assess the associations between circRNA expression and overall survival (OS), as well as clinicopathological parameters.A total of 111 eligible studies were included in this meta-analysis.High expression of oncogenic circRNAs was significantly associated with worse OS (HR = 1.90, 96% CI: 1.72-2.22;P < 0.001), while elevated tumorsuppressor circRNAs showed a non-significant protective trend (HR = 0.74, 95% CI: 0.54-1.03;P > 0.05).Upregulated circRNAs were also significantly correlated with advanced TNM stage (OR = 2.68, 95% CI: 2.09-3.45)and larger tumor size (OR = 1.52, 95% CI: 1.16-1.98).Conversely, downregulated circRNAs showed an inverse association with advanced TNM stage (OR = 0.44, 95% CI: 0.25-0.79)and tumor size (OR = 0.51, 95% CI: 0.34-0.77).High heterogeneity (I² > 50%) was observed, likely due to diverse cancer types and detection methods, but sensitivity analyses confirmed the result robustness.Egger's test indicated potential publication bias (P < 0.05).Mechanistically, circRNAs influence prognosis via miRNA sponging, RNA-binding protein interactions, and transcriptional regulation.This meta-analysis provides robust evidence that aberrant circRNA expression is associated with aggressive tumor characteristics and poor prognosis in digestive system cancers.However, clinical translation is limited by non-standardized detection methods and reliance on tissue-based assays.Large-scale, multicenter studies with standardized detection protocols and liquid biopsy validation are required to establish circRNAs as non-invasive prognostic biomarkers.