Diagnostic Accuracy of CircRNAs for Detecting Gastrointestinal Cancers: An Updated Meta-analysis

Gastrointestinal (GI) cancers remain a leading cause of cancer-related mortality worldwide, underscoring the urgent need for reliable, non-invasive diagnostic biomarkers. Circular RNAs (circRNAs), characterized by high stability and tissue specificity, have emerged as promising molecular indicators for early cancer detection. This study aimed to evaluate the diagnostic accuracy of circular RNAs (circRNAs) for detecting gastrointestinal (GI) cancers, including gastric cancer (GC), hepatocellular carcinoma (HCC), esophageal cancer (EC), colorectal cancer (CRC), and pancreatic cancer (PC).

A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and EMBASE up to December 2024, following PRISMA guidelines. Quality assessment was performed using the QUADAS-2 tool. Diagnostic accuracy metrics were analyzed using Metandi and Midas modules in STATA 17.

From 9,733 retrieved articles, 139 studies involving 25,847 participants and 153 circRNAs met inclusion/exclusion criteria. No new eligible studies were identified from July 2021 to December 2024. The pooled diagnostic performance of circRNAs for gastrointestinal cancers was: sensitivity 0.78 (95% CI: 0.76-0.79), specificity 0.76 (95% CI: 0.74-0.77), PLR 3.3 (95% CI: 3.1-3.5), NLR 0.29 (95% CI: 0.27-0.31), and AUC 0.83 (95% CI: 0.80-0.85). Specific circRNAs (e.g., hsa_circ_0001017, circ-SLC7A5, circ-LDLRAD3) showed promising diagnostic performance.

CircRNAs exhibit good diagnostic accuracy for hepatocellular carcinoma (AUC 0.83) and esophageal cancer (AUC 0.81), moderate-to-good accuracy for gastric cancer (AUC 0.79) and pancreatic cancer (AUC 0.78), but limited accuracy for colorectal cancer (AUC 0.68), highlighting their potential as non-invasive biomarkers, particularly for HCC and EC, with further validation needed to enhance clinical utility.