en Medical Biology Medical Biology مقاله مروری Review Article <p style="text-align: justify;"><span style="font-size:16px;"><span style="font-family:Times New Roman;"><span style="color:black">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 meta-analysis 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&ndash;2.22; P < 0.001), while elevated tumor-suppressor circRNAs showed a non-significant protective trend (HR = 0.74, 95% CI: 0.54&ndash;1.03; P > 0.05). Upregulated circRNAs were also significantly correlated with advanced TNM stage (OR = 2.68, 95% CI: 2.09&ndash;3.45) and larger tumor size (OR = 1.52, 95% CI: 1.16&ndash;1.98). Conversely, downregulated circRNAs showed&nbsp;an inverse association with advanced TNM stage (OR = 0.44, 95% CI: 0.25&ndash;0.79) and tumor size (OR = 0.51, 95% CI: 0.34&ndash;0.77). High heterogeneity (I&sup2; > 50%) was observed, likely due to diverse cancer types and detection methods, but sensitivity analyses confirmed the result robustness. Egger&rsquo;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.</span></span></span></p> Circular RNA, Digestive System Neoplasms, Meta-analysis, Prognosis, Biomarkers 249 264 http://journal.zums.ac.ir/browse.php?a_code=A-10-7215-1&slc_lang=en&sid=1 Fatemeh Shams shams8869@yahoo.com 5200319475328460085794 5200319475328460085794 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad-Hassan Arjmand arjmndmh@mums.ac.ir 5200319475328460085795 5200319475328460085795 No Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran Elnaz Zahiri zahirie2@mums.ac.ir 5200319475328460085796 5200319475328460085796 No Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran Hassan Mehrad-Majd mehradmajdh@mums.ac.ir 5200319475328460085797 5200319475328460085797 Yes Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran