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Sepsis Related Whole Blood MicroRNA Markers and Mediation in Acute Respiratory Distress Syndrome
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A7540 - Sepsis Related Whole Blood MicroRNA Markers and Mediation in Acute Respiratory Distress Syndrome
Author Block: L. Su1, Z. Zhu2, P. Tejera2, D. C. Christiani3; 1Environmental Health, Harvard Sch of Public Health, Boston, MA, United States, 2Environmental Health, Harvard T.H.Chan School of Public Health, Boston, MA, United States, 3Environmental Health, Harvard Sch of Public Hlth, Boston, MA, United States.
Rationale: Sepsis is a potentially life-threatening complication of a severe infection, when mediators are released into the bloodstream in response to the infection and trigger inflammation throughout the body. This inflammation can trigger a cascade of changes that can damage multiple organ systems, causing them to fail. MicroRNAs (miRNAs) mediate inflammation and infection, common manifestations of sepsis. We examined whether miRNAs from whole blood are potential biomarkers for sepsis in critically-ill patients.
Method: This case-control study (N=156) included sepsis patients and critically ill at-risk controls. Whole blood miRNAs were profiled and logistic regression analyses were performed to identify miRNA association with sepsis. Selected miRNAs were combined as a miRNA index score for sepsis by using the residuals of a significant miRNAs logistic regression model predicting for sepsis. The residuals were transformed to approximate normality using inverse normal scores to avoid potential outliers. A mediation analysis was performed to evaluate the connection between sepsis and acute respiratory distress syndrome (ARDS) through potential mediator effect of miRNA score.
Main Results: Statistical analysis was performed on 294 miRNAs. Logistic regression identified 5 miRNAs from the 156-patient cohort as potential biomarkers of ARDS (miR-24, OR=0.37, P=0.01; miR-766, OR=1.66, P=0.02; miR-449, OR=0.57, P=0.03; miR-34a, OR=0.04, P=0.01; let-7c, OR=0.67, P=0.05;). These 5 miRNAs were then combined into a miRNA score as described above. Mediation analysis showed there is a marginal significant direct effect between sepsis and ARDS (P=0.053), also a significant total effect of sepsis to ARDS through a mediating miRNA score (P=0.042).
Conclusions: Whole blood miRNA profiling revealed that miR-24, miR-766, miR-449, miR-34a and let-7c are potential biomarkers of sepsis. By combining these miRNAs into a miRNA score, we found a significant total effect of sepsis to ARDS mediated through the miRNA score.
Author Block: L. Su1, Z. Zhu2, P. Tejera2, D. C. Christiani3; 1Environmental Health, Harvard Sch of Public Health, Boston, MA, United States, 2Environmental Health, Harvard T.H.Chan School of Public Health, Boston, MA, United States, 3Environmental Health, Harvard Sch of Public Hlth, Boston, MA, United States.
Rationale: Sepsis is a potentially life-threatening complication of a severe infection, when mediators are released into the bloodstream in response to the infection and trigger inflammation throughout the body. This inflammation can trigger a cascade of changes that can damage multiple organ systems, causing them to fail. MicroRNAs (miRNAs) mediate inflammation and infection, common manifestations of sepsis. We examined whether miRNAs from whole blood are potential biomarkers for sepsis in critically-ill patients.
Method: This case-control study (N=156) included sepsis patients and critically ill at-risk controls. Whole blood miRNAs were profiled and logistic regression analyses were performed to identify miRNA association with sepsis. Selected miRNAs were combined as a miRNA index score for sepsis by using the residuals of a significant miRNAs logistic regression model predicting for sepsis. The residuals were transformed to approximate normality using inverse normal scores to avoid potential outliers. A mediation analysis was performed to evaluate the connection between sepsis and acute respiratory distress syndrome (ARDS) through potential mediator effect of miRNA score.
Main Results: Statistical analysis was performed on 294 miRNAs. Logistic regression identified 5 miRNAs from the 156-patient cohort as potential biomarkers of ARDS (miR-24, OR=0.37, P=0.01; miR-766, OR=1.66, P=0.02; miR-449, OR=0.57, P=0.03; miR-34a, OR=0.04, P=0.01; let-7c, OR=0.67, P=0.05;). These 5 miRNAs were then combined into a miRNA score as described above. Mediation analysis showed there is a marginal significant direct effect between sepsis and ARDS (P=0.053), also a significant total effect of sepsis to ARDS through a mediating miRNA score (P=0.042).
Conclusions: Whole blood miRNA profiling revealed that miR-24, miR-766, miR-449, miR-34a and let-7c are potential biomarkers of sepsis. By combining these miRNAs into a miRNA score, we found a significant total effect of sepsis to ARDS mediated through the miRNA score.
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