Fei Ye

Early detection is critical for improving pancreatic cancer prognosis. Our study aims to identify circulating microRNAs (miRNAs) associated with pancreatic cancer risk. The two‐stage study used plasma samples collected ≤5 years prior to cancer diagnosis, from case–control studies nested in five prospective cohort studies. The discovery stage included 185 case–control pairs from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Replication stage samples comprised 277 pairs from Shanghai Women's Health Study/Shanghai Men's Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study. Seven hundred and ninety‐eight miRNAs were measured using the NanoString nCounter Analysis System. Odds ratios (OR) and 95% confidence intervals (CI) for per 10% change in miRNAs in association with pancreatic cancer risk were derived from conditional logistic regression analysis in discovery and replication studies, separately, and then meta‐analyzed. Stratified analysis was conducted by age at diagnosis (<65/≥65 years) and time interval between sample collection and diagnosis (≤2/>2 years). In the discovery stage, 120 risk associated miRNAs were identified at p < .05. Three were validated in the replication stage: hsa‐miR‐199a‐3p/hsa‐miR‐199b‐3p, hsa‐miR‐767‐5p, and hsa‐miR‐191‐5p, with respective ORs (95% CI) being 0.89 (0.84–0.95), 1.08 (1.02–1.13), and 0.90 (0.85–0.95). Five additional miRNAs, hsa‐miR‐640, hsa‐miR‐874‐5p, hsa‐miR‐1299, hsa‐miR‐22‐3p, and hsa‐miR‐449b‐5p, were validated among patients diagnosed at ≥65 years, with OR (95% CI) of 1.23 (1.09–1.39), 1.33 (1.16–1.52), 1.25 (1.09–1.43), 1.28 (1.12–1.46), 0.76 (0.65–0.89), and 1.22 (1.07–1.39), respectively. The miRNA targets were enriched in pancreatic carcinogenesis/progression‐related pathways. Our study suggests that circulating miRNAs may identify individuals at high risk for pancreatic cancer ≤5 years prior to diagnosis, indicating its potential utility in cancer screening and surveillance.