A Novel Serum Exosomal MicroRNA Signature in the Early Prediction of Persistent Organ Failure in Patients With Acute Pancreatitis

OBJECTIVE: To investigate whether serum exosomal microRNAs (miRNAs) could be potential biomarkers in predicting acute pancreatitis (AP) with persistent organ failure (POF) at an early phase. BACKGROUND: Novel biomarkers are sorely needed for early prediction of POF in patients with AP. METHODS: In the discovery stage, exosomal miRNAs were profiled in sera from APs with or without POF (5 vs 5) using microarrays. POF-associated miRNA signatures then were assessed in the training cohort (n = 227) and further validated in 3 independent cohorts (n = 516), including one nested case-control cohort. RESULTS: A total of 743 APs were recruited in this large-scale biomarker identification study with a nested case-control study. Data from the discovery cohort demonstrated that 90 exosomal miRNAs were significantly dysregulated in APs with POF compared with controls. One miRNA classifier (Cmi) comprising 3 miRNAs (miR-4265, 1208, 3127-5p) was identified in the training cohort and was further evaluated in 2 validation cohorts for their predictive value for POF. Area under the curves for Cmi ranged from 0.88 to 0.90, which was statistically superior to area under the curves of Acute Physiology and Chronic Health Examination-II and bedside index for severity in AP, and outperformed blood urea nitrogen and creatinine in POF prediction across all cohorts ( P < 0.05). Higher levels of Cmi indicated an increased need for intensive care unit admission, prolonged hospitalization, and elevated mortality rate, thus poor prognosis. In the nested case-control study, Cmi could help identify prediagnostic POF in postendoscopic retrograde cholangiopancreatography pancreatitis cases within "golden hours" after endoscopic retrograde cholangiopancreatography with high efficacy. CONCLUSIONS: Serum exosomal Cmi may be an early predictor for POF in AP, even within "golden hours" after AP onset. TRAIL REGISTRATION: ClinicalTrials.gov (NCT02602808).