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A Quantitative Detection Method for MicroRNAs in the Kidney of an Ischemic Kidney Injury Mouse Model
Published on: September 11, 2020
Cellular microRNAs correlate with clinical parameters in multiple injury patients
Diego A Vicente1, Seth A Schobel, Simone Anfossi
1From the Surgical Critical Care Initiative (D.A.V., S.A.S., F.L., V.K., M.J.B., T.G.B., T.A.D., C.J.D., A.D.K., E.A.E.); Department of Surgery (D.A.V., S.A.S., F.L., H.R., V.K., M.J.B., T.A.D., E.A.E.), Uniformed Services University of the Health Sciences; Henry M Jackson Foundation for the Advancement of Military Medicine (S.A.S., F.L., V.K.), Bethesda, Maryland; Translational Molecular Pathology (S.A., M.S., G.A.C.), Houston, Texas; DecisionQ (H.H.), Arlington, Virginia; Department of Surgery (F.L., V.K., M.J.B., E.A.E.), Walter Reed National Military Medical Center, Bethesda, Maryland; Department of Surgery (T.G.B., C.J.D.), Emory University, Atlanta, Georgia; and Department of Surgery (A.D.K.), Duke University, Durham, North Carolina.
Introduction:
The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may modulate the inflammatory response. The authors hypothesize that the expression of microRNAs would correlate to complicated recoveries in polytrauma patients (PtPs).
Methods:
Polytrauma patients enrolled in the prospective observational Tissue and Data Acquisition Protocol with Injury Severity Score of >15 were selected for this study. Polytrauma patients were divided into complicated recoveries and uncomplicated recovery groups. Polytrauma patients' blood samples were obtained at the time of admission (T0). Established biomarkers of systemic inflammation, including cytokines and chemokines, were measured using multiplexed Luminex-based methods, and novel microRNAs were measured in plasma samples using multiplex RNA hybridization.
Results:
Polytrauma patients (n = 180) had high Injury Severity Score (26 [20-34]) and complicated recovery rate of 33%. MicroRNAs were lower in PtPs at T0 compared with healthy controls, and bivariate analysis demonstrated that variations of microRNAs correlated with age, race, comorbidities, venous thromboembolism, pulmonary complications, complicated recovery, and mortality. Positive correlations were noted between microRNAs and interleukin 10, vascular endothelial growth factor, Acute Physiology and Chronic Health Evaluation, and Sequential Organ Failure Assessment scores. Multivariable Lasso regression analysis of predictors of complicated recovery based on microRNAs, cytokines, and chemokines revealed that miR-21-3p and monocyte chemoattractant protein-1 were predictive of complicated recovery with an area under the curve of 0.78.
Conclusion:
Systemic microRNAs were associated with poor outcomes in PtPs, and results are consistent with previously described trends in critically ill patients. These early biomarkers of inflammation might provide predictive utility in early complicated recovery diagnosis and prognosis. Because of their potential to regulate immune responses, microRNAs may provide therapeutic targets for immunomodulation.
Level Of Evidence:
Diagnostic Tests/Criteria; Level II.
Insights
MicroRNAs in polytrauma patients correlate with complicated recoveries. Lower microRNA levels and specific markers like miR-21-3p may predict poor outcomes, offering potential therapeutic targets for immunomodulation.
Area of Science:
- Trauma and Critical Care Medicine
- Molecular Biology and Genetics
- Immunology
Background:
- The inflammatory response in polytrauma is complex and linked to injury severity and patient outcomes.
- MicroRNAs (miRNAs) are implicated in modulating immune responses, particularly in infection-mediated pathways.
- The role of miRNA expression in predicting recovery in polytrauma patients remains an area of investigation.
Purpose of the Study:
- To investigate the hypothesis that microRNA expression correlates with complicated recoveries in polytrauma patients (PtPs).
- To identify potential early biomarkers for predicting recovery and prognosis in critically ill trauma patients.
- To explore miRNAs as potential therapeutic targets for immunomodulation in polytrauma.
Main Methods:
- Prospective observational study of 180 polytrauma patients with Injury Severity Score >15.
- Categorization of patients into complicated and uncomplicated recovery groups.
- Measurement of plasma microRNAs and systemic inflammation biomarkers (cytokines, chemokines) at admission (T0) using multiplexed methods.
Main Results:
- Polytrauma patients exhibited lower microRNA levels compared to healthy controls.
- Bivariate analysis showed correlations between microRNA variations and factors including age, comorbidities, complications, and mortality.
- Multivariable analysis identified miR-21-3p and monocyte chemoattractant protein-1 as predictors of complicated recovery (AUC=0.78).
Conclusions:
- Systemic microRNAs are associated with adverse outcomes in polytrauma patients.
- Early detection of microRNA profiles may aid in diagnosing and prognosing complicated recoveries.
- MicroRNAs hold potential as therapeutic targets for modulating immune responses in trauma patients.

