Cellular microRNAs correlate with clinical parameters in multiple injury patients

• Type of Material: Article
• Authors: Diego A Vicente, Uniformed Services University of the Health Sciences; Seth A Schobel, Uniformed Services University of the Health Sciences; Simone Anfossi, Translational Molecular Pathology; Hannah Hensman, DecisionQ; Felipe Lisboa, Uniformed Services University of the Health Sciences; Henry Robertson, Uniformed Services University of the Health Sciences; Vivek Khatri, Uniformed Services University of the Health Sciences; Matthew J Bradley, Uniformed Services University of the Health Sciences; Masayoshi Shimizu, Translational Molecular Pathology; Timothy Buchman, Emory University; Thomas A Davis, Uniformed Services University of the Health Sciences; Christopher Dente, Emory University; Allan Kirk, Emory University; George A Calin, Translational Molecular Pathology; Eric A Elster, Uniformed Services University of the Health Sciences
• Language: English
• Date: 2022-10-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2022, Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.
• Final Published Version (URL): http://dx.doi.org/10.1097/TA.0000000000003708
• Title of Journal or Parent Work: JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
• Volume: 93
• Issue: 4
• Start Page: 427
• End Page: 438
• Keywords: MIR-21; Surgery; Science & Technology; RNAS; Trauma; Life Sciences & Biomedicine; General & Internal Medicine; complications; SEPSIS; Critical Care Medicine; microRNA; recovery; inflammation

Abstract

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.