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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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Dynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levelsDynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levels on day 1 (D1), day 3 (D3), day 5(D5), day 7 (D7), day 10 (D10) and day 14 (D14) after admission in survivors (n=11)and non-survivors (n=10). The data are shown as means and the error bars indicateS.D. *P<0.05 and **P<0.01.
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Figure 7: Dynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levelsDynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levels on day 1 (D1), day 3 (D3), day 5(D5), day 7 (D7), day 10 (D10) and day 14 (D14) after admission in survivors (n=11)and non-survivors (n=10). The data are shown as means and the error bars indicateS.D. *P<0.05 and **P<0.01.

Mentions: Dynamic changes in serum ACVR2A, FOXO1, IHH and STK4 levels in patients with sepsis during theirhospitalization in ICUs were evaluated. The 21 patients with sepsis were separated into a group often non-survivors (two with mild sepsis, four with severe sepsis and four with septic shock) and agroup of 11 survivors (four with mild sepsis, five with severe sepsis and two with septic shock)according to 28-day mortality. As shown in Figure 7, the serumlevels of FOXO1, ACVR2A and IHH in the surviving group were significantly higher than those in thenon-surviving group at all time points (P<0.001). The levels ofFOXO1 in the non-surviving group showed a significantly decreasing trend over time, whereasthe expression levels of FOXO1 in the surviving group tended to significantly increase duringhospitalization in the ICU (P<0.05). Unlike FOXO1, ACVR2A showed a reversedtendency over time, with a significantly increasing trend in the non-surviving group and asignificantly decreasing trend in the surviving group (P<0.05). For STK4,except for the first three time points, no significant difference was present between the survivorsand non-survivors.


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)

Dynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levelsDynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levels on day 1 (D1), day 3 (D3), day 5(D5), day 7 (D7), day 10 (D10) and day 14 (D14) after admission in survivors (n=11)and non-survivors (n=10). The data are shown as means and the error bars indicateS.D. *P<0.05 and **P<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Dynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levelsDynamic changes of serum FOXO1, ACVR2A, IHH and STK4 levels on day 1 (D1), day 3 (D3), day 5(D5), day 7 (D7), day 10 (D10) and day 14 (D14) after admission in survivors (n=11)and non-survivors (n=10). The data are shown as means and the error bars indicateS.D. *P<0.05 and **P<0.01.
Mentions: Dynamic changes in serum ACVR2A, FOXO1, IHH and STK4 levels in patients with sepsis during theirhospitalization in ICUs were evaluated. The 21 patients with sepsis were separated into a group often non-survivors (two with mild sepsis, four with severe sepsis and four with septic shock) and agroup of 11 survivors (four with mild sepsis, five with severe sepsis and two with septic shock)according to 28-day mortality. As shown in Figure 7, the serumlevels of FOXO1, ACVR2A and IHH in the surviving group were significantly higher than those in thenon-surviving group at all time points (P<0.001). The levels ofFOXO1 in the non-surviving group showed a significantly decreasing trend over time, whereasthe expression levels of FOXO1 in the surviving group tended to significantly increase duringhospitalization in the ICU (P<0.05). Unlike FOXO1, ACVR2A showed a reversedtendency over time, with a significantly increasing trend in the non-surviving group and asignificantly decreasing trend in the surviving group (P<0.05). For STK4,except for the first three time points, no significant difference was present between the survivorsand non-survivors.

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