BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest malignancies, with limited survival benefits despite recent therapeutic advances. Few prognostic biomarkers are available for PDAC monitoring in clinical practice. We conducted a meta-analysis to evaluate and synthesise evidence on the prognostic significance of miRNA expression in PDAC. METHODS: The protocol was registered with PROSPERO (CRD42023463542). We conducted a systematic search in PubMed, CENTRAL, and Embase on January 27, 2026, to identify studies assessing miRNA expression levels in patients with PDAC with reported overall survival (OS) or progression-free survival (PFS) outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Prediction intervals (PI) were reported if feasible. Separate analyses were performed by miRNA functional categories: oncogenic, tumour suppressor, chemoresistance-related, metastasis-related, and dual-role miRNAs. FINDINGS: range 0-94%). miRNA-21 was the most frequently studied individual biomarker and showed a consistent association with worse multivariate OS (HR 2.24, 95% CI 1.95-2.57; 95% PI 1.92-2.61). INTERPRETATION: Elevated expression of oncogenic and chemoresistance-related miRNAs is associated with worse survival outcomes in PDAC. However, substantial heterogeneity and wide prediction intervals observed in several pooled analyses indicate variability in effect sizes across studies. Among the investigated biomarkers, miRNA-21 has shown the most consistent prognostic association and may represent the strongest candidate for future clinical implementation. Further validation and standardisation are required before miRNA profiling can be integrated into routine clinical practice.
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Ulmann et al. (2026) studied this question.
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