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Serum microRNA signatures identified by Solexa sequencing predict sepsis patients' mortality: a prospective observational study.

Wang H, Zhang P, Chen W, Feng D, Jia Y, Xie L - PLoS ONE (2012)

Bottom Line: An analysis was done using these seven variables combined.The AUC for these combined variables' predictive probability was 0.953 (95% CI: 0.923-0.983), which was much higher than the AUCs for Acute Physiology and Chronic Health Evaluation II scores (0.782; 95% CI: 0.712-0.851), Sequential Organ Failure Assessment scores (0.752; 95% CI: 0.672-0.832), and procalcitonin levels (0.689; 95% CI: 0.611-0.784).With a cut-off point of 0.550, the predictive value of the seven variables had a sensitivity of 88.5% and a specificity of 90.4%.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan Province, China.

ABSTRACT

Background: Sepsis is the leading cause of death in Intensive Care Units. Novel sepsis biomarkers and targets for treatment are needed to improve mortality from sepsis. MicroRNAs (miRNAs) have recently been used as finger prints for sepsis, and our goal in this prospective study was to investigate if serum miRNAs identified in genome-wide scans could predict sepsis mortality.

Methodology/principal findings: We enrolled 214 sepsis patients (117 survivors and 97 non-survivors based on 28-day mortality). Solexa sequencing followed by quantitative reverse transcriptase polymerase chain reaction assays was used to test for differences in the levels of miRNAs between survivors and non-survivors. miR-223, miR-15a, miR-16, miR-122, miR-193*, and miR-483-5p were significantly differentially expressed. Receiver operating characteristic curves were generated and the areas under the curve (AUC) for these six miRNAs for predicting sepsis mortality ranged from 0.610 (95%CI: 0.523-0.697) to 0.790 (95%CI: 0.719-0.861). Logistic regression analysis showed that sepsis stage, Sequential Organ Failure Assessment scores, Acute Physiology and Chronic Health Evaluation II scores, miR-15a, miR-16, miR-193b*, and miR-483-5p were associated with death from sepsis. An analysis was done using these seven variables combined. The AUC for these combined variables' predictive probability was 0.953 (95% CI: 0.923-0.983), which was much higher than the AUCs for Acute Physiology and Chronic Health Evaluation II scores (0.782; 95% CI: 0.712-0.851), Sequential Organ Failure Assessment scores (0.752; 95% CI: 0.672-0.832), and procalcitonin levels (0.689; 95% CI: 0.611-0.784). With a cut-off point of 0.550, the predictive value of the seven variables had a sensitivity of 88.5% and a specificity of 90.4%. Additionally, miR-193b* had the highest odds ratio for sepsis mortality of 9.23 (95% CI: 1.20-71.16).

Conclusion/significance: Six serum miRNA's were identified as prognostic predictors for sepsis patients.

Trial registration: ClinicalTrials.gov NCT01207531.

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Related in: MedlinePlus

Receiver operating characteristic (ROC) curves for serum miRNAs and clinically used indicators for sepsis non-survivors (n = 73) and survivors (n = 93).Serum levels of miRNAs were quantified using real time qPCR. Each qPCR was done in triplicate in 96-well plates. Expression levels of the selected miRNAs were normalized to U6 snRNA and presented as fold-changes (2-ΔΔCt) above normal controls.
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pone-0038885-g004: Receiver operating characteristic (ROC) curves for serum miRNAs and clinically used indicators for sepsis non-survivors (n = 73) and survivors (n = 93).Serum levels of miRNAs were quantified using real time qPCR. Each qPCR was done in triplicate in 96-well plates. Expression levels of the selected miRNAs were normalized to U6 snRNA and presented as fold-changes (2-ΔΔCt) above normal controls.

Mentions: To investigate the predictive mortality value of the six confirmed miRNAs, receiver operating characteristic (ROC) curves were generated and the areas under the curves (AUCs) were calculated. The AUCs for the six miRNAs ranged from 0.610 (95%CI: 0.523–0.697) to 0.790 (95%CI: 0.719–0.861) (Figure 3). The AUCs for SOFA scores, APACHE II scores, and PCT levels were, respectively, 0.782 (95%CI: 0.712–0.851), 0.752 (95%CI: 0.672–0.832), and 0.689 (95%CI: 0.611–0.784) (Figure 4). The AUC for miR-193b* had the highest value, followed by those for SOFA scores and miR-16. AUCs for miR-223 and miR-122 were nearly identical to the AUC for APACHE II scores.


Serum microRNA signatures identified by Solexa sequencing predict sepsis patients' mortality: a prospective observational study.

Wang H, Zhang P, Chen W, Feng D, Jia Y, Xie L - PLoS ONE (2012)

Receiver operating characteristic (ROC) curves for serum miRNAs and clinically used indicators for sepsis non-survivors (n = 73) and survivors (n = 93).Serum levels of miRNAs were quantified using real time qPCR. Each qPCR was done in triplicate in 96-well plates. Expression levels of the selected miRNAs were normalized to U6 snRNA and presented as fold-changes (2-ΔΔCt) above normal controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376145&req=5

pone-0038885-g004: Receiver operating characteristic (ROC) curves for serum miRNAs and clinically used indicators for sepsis non-survivors (n = 73) and survivors (n = 93).Serum levels of miRNAs were quantified using real time qPCR. Each qPCR was done in triplicate in 96-well plates. Expression levels of the selected miRNAs were normalized to U6 snRNA and presented as fold-changes (2-ΔΔCt) above normal controls.
Mentions: To investigate the predictive mortality value of the six confirmed miRNAs, receiver operating characteristic (ROC) curves were generated and the areas under the curves (AUCs) were calculated. The AUCs for the six miRNAs ranged from 0.610 (95%CI: 0.523–0.697) to 0.790 (95%CI: 0.719–0.861) (Figure 3). The AUCs for SOFA scores, APACHE II scores, and PCT levels were, respectively, 0.782 (95%CI: 0.712–0.851), 0.752 (95%CI: 0.672–0.832), and 0.689 (95%CI: 0.611–0.784) (Figure 4). The AUC for miR-193b* had the highest value, followed by those for SOFA scores and miR-16. AUCs for miR-223 and miR-122 were nearly identical to the AUC for APACHE II scores.

Bottom Line: An analysis was done using these seven variables combined.The AUC for these combined variables' predictive probability was 0.953 (95% CI: 0.923-0.983), which was much higher than the AUCs for Acute Physiology and Chronic Health Evaluation II scores (0.782; 95% CI: 0.712-0.851), Sequential Organ Failure Assessment scores (0.752; 95% CI: 0.672-0.832), and procalcitonin levels (0.689; 95% CI: 0.611-0.784).With a cut-off point of 0.550, the predictive value of the seven variables had a sensitivity of 88.5% and a specificity of 90.4%.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan Province, China.

ABSTRACT

Background: Sepsis is the leading cause of death in Intensive Care Units. Novel sepsis biomarkers and targets for treatment are needed to improve mortality from sepsis. MicroRNAs (miRNAs) have recently been used as finger prints for sepsis, and our goal in this prospective study was to investigate if serum miRNAs identified in genome-wide scans could predict sepsis mortality.

Methodology/principal findings: We enrolled 214 sepsis patients (117 survivors and 97 non-survivors based on 28-day mortality). Solexa sequencing followed by quantitative reverse transcriptase polymerase chain reaction assays was used to test for differences in the levels of miRNAs between survivors and non-survivors. miR-223, miR-15a, miR-16, miR-122, miR-193*, and miR-483-5p were significantly differentially expressed. Receiver operating characteristic curves were generated and the areas under the curve (AUC) for these six miRNAs for predicting sepsis mortality ranged from 0.610 (95%CI: 0.523-0.697) to 0.790 (95%CI: 0.719-0.861). Logistic regression analysis showed that sepsis stage, Sequential Organ Failure Assessment scores, Acute Physiology and Chronic Health Evaluation II scores, miR-15a, miR-16, miR-193b*, and miR-483-5p were associated with death from sepsis. An analysis was done using these seven variables combined. The AUC for these combined variables' predictive probability was 0.953 (95% CI: 0.923-0.983), which was much higher than the AUCs for Acute Physiology and Chronic Health Evaluation II scores (0.782; 95% CI: 0.712-0.851), Sequential Organ Failure Assessment scores (0.752; 95% CI: 0.672-0.832), and procalcitonin levels (0.689; 95% CI: 0.611-0.784). With a cut-off point of 0.550, the predictive value of the seven variables had a sensitivity of 88.5% and a specificity of 90.4%. Additionally, miR-193b* had the highest odds ratio for sepsis mortality of 9.23 (95% CI: 1.20-71.16).

Conclusion/significance: Six serum miRNA's were identified as prognostic predictors for sepsis patients.

Trial registration: ClinicalTrials.gov NCT01207531.

Show MeSH
Related in: MedlinePlus