Prognostic and clinicopathological significance of circular RNA expression in cholangiocarcinoma: a systematic review and meta-analysis

Purpose Circular RNAs (circRNAs) are aberrantly expressed in various human cancers and regulate tumor cell proliferation, invasion, and metastasis through multiple mechanisms. However, existing studies are mostly single-center with small sample sizes, lacking systematic quantitative evaluation. This systematic review and meta-analysis aims to clarify the association between circRNA expression levels and prognosis as well as clinicopathological features in patients with cholangiocarcinoma (CCA). Materials and methods Two researchers independently searched Web of Science and PubMed databases to identify studies evaluating the relationship between circRNA expression and prognosis or pathological features of CCA, with the final search date of September 28, 2025. Literature screening was performed based on predefined inclusion criteria (cohort or case-control design; RT-qPCR detection of circRNA; available clinicopathological data) and exclusion criteria (duplicate data, reviews, non-human studies, non-English/Chinese publications). Risk of bias was assessed using the Newcastle-Ottawa Scale, and statistical analysis was conducted in StataSE 12.0 using the random-effects model for all primary meta-analyses.This study is registered on PROSPERO, number CRD420261352256. Results A total of 46 studies involving 3,416 CCA patients from China and a multinational cohort (France/Spain) were included. All studies used qRT-PCR; high-expression and low-expression groups were defined using various cut-off criteria including median, mean, X-tile, and Youden index derived from ROC analysis.The meta-analysis showes that high expression of oncogenic circRNAs is associated with poorer overall survival (HR = 2.27, 95% CI: 2.02–2.55), and high expression of tumor-suppressive circRNAs is linked to favorable prognosis (HR = 0.53, 95% CI: 0.47–0.60). CircRNA expression is not significantly correlated with age, CA19-9 or gender, but is significantly associated with tumor differentiation (OR = 1.72), lymph node metastasis (OR = 3.43), TNM stage (OR = 2.91). Conclusion This meta-analysis indicates that dysregulated expression of circRNAs is closely associated with malignant progression of CCA and these molecules might represent candidate prognostic markers requiring further validation. However, the evidence has limitations including geographic bias (mostly Chinese studies), heterogeneity in cut-off values, and potential publication bias. Large-scale, well-designed studies are still needed to verify their actual clinical utility.