A Combined Score of Circulating miRNAs Allows Outcome Prediction in Critically Ill Patients.

Background and aims: Identification of patients with increased risk of mortality represents an important prerequisite for an adapted adequate and individualized treatment of critically ill patients. Circulating micro-RNA (miRNA) levels have been suggested as potential biomarkers at the intensive care unit (ICU), but none of the investigated miRNAs displayed a sufficient sensitivity or specificity to be routinely employed as a single marker in clinical practice. Methods and results: We recently described alterations in serum levels of 7 miRNAs (miR-122, miR-133a, miR-143, miR-150, miR-155, miR-192, and miR-223) in critically ill patients at a medical ICU. In this study, we re-analyzed these previously published data and performed a combined analysis of these markers to unravel their potential as a prognostic scoring system in the context of critical illness. Based on the Youden's index method, cut-off values were systematically defined for dysregulated miRNAs, and a "miRNA survival score" was calculated. Patients with high scores displayed a dramatically impaired prognosis compared to patients with low values. Additionally, the predictive power of our score could be further increased when the patient's age was additionally incorporated into this score. Conclusions: We describe the first miRNA-based biomarker score for prediction of medical patients' outcome during and after ICU treatment. Adding the patients' age into this score was associated with a further increase in its predictive power. Further studies are needed to validate the clinical utility of this score in risk-stratifying critically ill patients.