Prognostic, Diagnostic, and Clinicopathological Significance of Circular RNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Growing evidence shows that circRNAs are closely associated with the clinicopathological characteristics of pancreatic cancer (PC) patients and might facilitate the early diagnosis and prediction of prognosis after surgery. In this study, we reviewed a total of 48 studies to examine the clinical value of circRNAs in PC. We found that differentially expressed circRNAs are significantly correlated with the prognosis and clinicopathological features of PC patients and could assist the diagnosis, suggesting circRNAs as potent biomarkers in PC. ABSTRACT: Pancreatic cancer (PC) is a highly aggressive malignant tumor with a high mortality rate. It is urgent to find optimal molecular targets for the early diagnosis and treatment of PC. Here, we aimed to systematically analyze the prognostic, diagnostic, and clinicopathological significance of circular RNAs (circRNAs) in PC. Relevant studies were screened through PubMed, Web of Science, and other databases. The prognostic value of PC-associated circRNAs was assessed using the composite hazard ratio (HR), the diagnostic performance was assessed using the area under the summary receiver operator characteristic (SROC) curve (AUC), and the correlation with clinicopathological characteristics using the composite odds ratio (OR) was explored. In our study, 48 studies were included: 34 for prognosis, 11 for diagnosis, and 30 for correlation with clinicopathological characteristics. For prognosis, upregulated circRNAs were associated with poorer overall survival (OS) (HR = 2.02) and disease-free survival/progression-free survival (HR = 1.84) while downregulated circRNAs were associated with longer OS (HR = 0.55). Notably, the combination of circRNAs, including hsa_circ_0064288, hsa_circ_0000234, hsa_circ_0004680, hsa_circ_0071036, hsa_circ_0000677, and hsa_circ_0001460, was associated with worse OS (HR = 2.35). For diagnosis, the AUC was 0.83, and the pooled sensitivity and specificity were 0.79 and 0.73, respectively. For clinicopathologic characteristics, upregulated circRNAs were associated with poorer tumor differentiation, more nerve and vascular invasion, higher T stage, lymphatic metastasis, distant metastasis, advanced TNM stage, and higher preoperative CA19-9 level. In contrast, downregulated circRNAs were negatively associated with PC differentiation and lymphatic metastasis. Overall, our results showed that circRNAs are closely related to the prognosis and clinicopathological characteristics of PC patients and could be utilized for early diagnosis; thus, they are promising biomarkers for clinical application in PC.