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Nucleotide motif-guided selection of plasma microRNA biomarkers for organ injury prediction in trauma
Boyang Ren1, Chien-Yu Lin2, Ruoxing Li1
1Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine; Baltimore, MD, USA.
Background:
Trauma remains a leading cause of morbidity and mortality in part due to secondary organ injury and infection. Yet, our ability to predict the downstream pathophysiologic responses leading to organ injury and adverse outcomes is limited. Extracellular microRNAs (ex-miRNAs) as a DAMP can drive innate immune response and organ injury. Here, we tested plasma miRNAs as predictive biomarkers for organ injury in trauma.
Methods:
Twelve miRNAs were selected based on RNAseq and pro-inflammatory nucleotide motifs identified by machine learning. Digital PCR was employed to quantify plasma miRNAs and Luminex to measure trauma injury markers. Multivariate Random Forest models were built to assess the predictive performance of the miRNA biomarkers.
Results:
We identified a set of five nucleotide motifs that can predict the pro-inflammatory property of plasma miRNAs with a sensitivity of 84% and specificity of 69%. There was a marked and severity-dependent increase in the plasma miRNA biomarkers and numerous trauma injury markers at time of admission. The plasma concentrations of these miRNA biomarkers were highly correlated with the injury markers linked to various trauma endotypes. AUROC analyses indicated that the miRNA biomarkers possess strong diagnostic abilities and prediction in overall severity, organ injury, metabolic acidosis, coagulopathy, and innate inflammation in the trauma (n=48) but not sepsis (n=47) cohort. In a combined cohort, miR-224-5p and miR-145-5p exhibited a superior performance in differential diagnosis of trauma and sepsis with AUROC of 0.90 and 0.91, respectively.
Conclusion:
The panel of plasma miRNAs are specific biomarkers with strong diagnostic and prognostic performance in trauma-induced organ injury.
Insights
New biomarkers, including specific microRNAs (miRNAs), show promise in predicting organ injury and immune responses after trauma. These findings could improve patient outcomes by enabling earlier risk assessment.
Area of Science:
- Biomarkers
- Trauma Pathophysiology
- Molecular Diagnostics
Background:
- Trauma is a major cause of death, often due to secondary multi-organ injury.
- Predicting trauma's downstream effects and patient outcomes remains challenging.
- MicroRNAs (miRNAs) are increasingly recognized as potential diagnostic and prognostic markers.
Purpose of the Study:
- To identify and validate plasma microRNAs (miRNAs) as biomarkers for predicting trauma-related pathophysiology and outcomes.
- To investigate the association of selected miRNAs with inflammatory markers and organ injury.
- To assess the predictive capability of these miRNAs for trauma severity and specific injuries.
Main Methods:
- Plasma RNA-sequencing (RNA-Seq) was used to identify candidate microRNA (miRNA) biomarkers.
- A machine learning algorithm identified unique pro-inflammatory nucleotide motifs.
- Candidate miRNAs were tested in a cohort of 48 blunt trauma patients for association with clinical markers and organ injury using Area Under the Receiver Operating Characteristic (AUROC) analysis.
Main Results:
- A panel of plasma miRNAs was significantly elevated in trauma patients upon admission.
- Elevated miRNA levels correlated strongly with markers of organ injury, coagulopathy, endothelial activation, and inflammation.
- AUROC analyses demonstrated the miRNAs' ability to predict trauma severity, brain and liver injury, metabolic acidosis, coagulopathy, and inflammation.
Conclusions:
- Selected plasma miRNAs show significant potential as biomarkers for predicting trauma pathophysiology and clinical outcomes.
- These miRNA biomarkers may aid in early risk stratification and management of trauma patients.
- Further research can explore the clinical utility of these miRNAs in trauma care.
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