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Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.

Wang HJ, Wang BZ, Zhang PJ, Deng J, Zhao ZR, Zhang X, Xiao K, Feng D, Jia YH, Liu YN, Xie LX - Clin. Sci. (2014)

Bottom Line: DUSP3 levels were not significantly different between any groups.When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%.Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points.

View Article: PubMed Central - PubMed

Affiliation: ‡Department of Respiratory Medicine, the Affiliated Beijing Tiantan Hospital of Capital Medical University, Beijing, 100050, China.

ABSTRACT
The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785-0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores.

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ROC curves for predictive probabilities, SOFA score, APACHE II score and PCT levels betweensurvivors (n=84) and non-survivors (n=41)
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Figure 6: ROC curves for predictive probabilities, SOFA score, APACHE II score and PCT levels betweensurvivors (n=84) and non-survivors (n=41)

Mentions: ROC analysis was then performed on ACVR2A, FOXO1, IHH and STK4 to evaluate the predictive valueof sepsis mortality. STK4 had the highest AUC of 0.751 (95% CI: 0.624–0.878) followed byFOXO1, IHH and ACVR2A with AUCs of 0.726 (95% CI: 0.636–0.816), 0.668 (95% CI:0.566–0.770) and 0.668 (95% CI: 0.564–0.772) respectively (Figure 5) (CI stands for confidence interval). Since these four proteins originatedfrom one miRNA profile, we entered them into a binary logistic regression analysis to obtainpredictive probabilities. ROC analysis was subsequently performed on the predictive probabilities;the AUC was 0.875 (95% CI: 0.785–0.965), which was higher than the SOFA score, APACHE IIscore and PCT, which had AUCs of 0.847 (95% CI: 0.776–0.918), 0.834 (95% CI:0.767–0.905) and 0.682 (95% CI: 0.529–0.835) respectively (Figure 6). When the value of the predictive probabilities was 0.449, the fourproteins yielded a sensitivity of 68 and a specificity of 91%. Then, the AIC value was alsocalculated for the four proteins, SOFA score, APACHE II score and PCT. The AIC values were−331, −234.75, −228.25 and −300.75 respectively. The four proteins havethe lowest AIC value, which meant that the four proteins had better prognostic value than othervalues.


Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.

Wang HJ, Wang BZ, Zhang PJ, Deng J, Zhao ZR, Zhang X, Xiao K, Feng D, Jia YH, Liu YN, Xie LX - Clin. Sci. (2014)

ROC curves for predictive probabilities, SOFA score, APACHE II score and PCT levels betweensurvivors (n=84) and non-survivors (n=41)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202716&req=5

Figure 6: ROC curves for predictive probabilities, SOFA score, APACHE II score and PCT levels betweensurvivors (n=84) and non-survivors (n=41)
Mentions: ROC analysis was then performed on ACVR2A, FOXO1, IHH and STK4 to evaluate the predictive valueof sepsis mortality. STK4 had the highest AUC of 0.751 (95% CI: 0.624–0.878) followed byFOXO1, IHH and ACVR2A with AUCs of 0.726 (95% CI: 0.636–0.816), 0.668 (95% CI:0.566–0.770) and 0.668 (95% CI: 0.564–0.772) respectively (Figure 5) (CI stands for confidence interval). Since these four proteins originatedfrom one miRNA profile, we entered them into a binary logistic regression analysis to obtainpredictive probabilities. ROC analysis was subsequently performed on the predictive probabilities;the AUC was 0.875 (95% CI: 0.785–0.965), which was higher than the SOFA score, APACHE IIscore and PCT, which had AUCs of 0.847 (95% CI: 0.776–0.918), 0.834 (95% CI:0.767–0.905) and 0.682 (95% CI: 0.529–0.835) respectively (Figure 6). When the value of the predictive probabilities was 0.449, the fourproteins yielded a sensitivity of 68 and a specificity of 91%. Then, the AIC value was alsocalculated for the four proteins, SOFA score, APACHE II score and PCT. The AIC values were−331, −234.75, −228.25 and −300.75 respectively. The four proteins havethe lowest AIC value, which meant that the four proteins had better prognostic value than othervalues.

Bottom Line: DUSP3 levels were not significantly different between any groups.When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%.Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points.

View Article: PubMed Central - PubMed

Affiliation: ‡Department of Respiratory Medicine, the Affiliated Beijing Tiantan Hospital of Capital Medical University, Beijing, 100050, China.

ABSTRACT
The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785-0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores.

Show MeSH
Related in: MedlinePlus