Association between circulating levels of miRNAs and pancreatic cancer risk through the years prior to pancreatic cancer diagnosis

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is critical to improve the prognosis. However, biomarkers for early diagnosis are lacking. Analysis of prediagnostic plasma samples and individually matched cancer-free controls from five prospective cohort studies found 20 miRNAs significantly associated with PDAC risk. Among them, 13 miRNAs showed a significant ratio change within 10 years prior to PDAC diagnosis. The case-control difference of miR-155-5p and miR-493-3p increased when blood draw was closer to diagnosis, whereas the ratio changes of the remaining 11 miRNAs decreased. Adding 13 miRNAs to known risk factors and CA19-9 significantly improved the prediction performance for imminent PDAC risk, with AUCs of 85%, 77%, and 73% during the time windows of 1, 2, and 3 years prior to PDAC diagnosis. The authors conclude that these results suggest a potential utility of monitoring circulating miRNAs for PDAC risk surveillance among high-risk individuals.