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

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.

SUBMITTER: Wang HJ

PROVIDER: S-EPMC4202716 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Wang Hui-juan HJ Wang Bao-zeng BZ Zhang Peng-jun PJ Deng Jie J Zhao Zhi-rui ZR Zhang Xin X Xiao Kun K Feng Dan D Jia Yan-hong YH Liu You-ning YN Xie Li-xin LX

Clinical science (London, England : 1979) 20140601 12

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 predic ...[more]

PMID: 24303815

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Project description:BACKGROUND:MiRNAs (microRNA) are 18-24?nt endogenous noncoding RNAs that regulate gene expression at the post-transcriptional level, including tissue-specific, developmental timing and evolutionary conservation gene expression. RESULTS:This study used high-throughput sequencing technology for the first time in Larix olgensis, predicted 78 miRNAs, including 12,229,003 reads sRNA, screened differentially expressed miRNAs. Predicting target genes was helpful for understanding the miRNA regulation function and obtained 333 corresponding target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation were analysed, mostly including nucleic acid binding, plant hormone signal transduction, pantothenate and CoA biosynthesis, and cellulose synthase. This study will lay the foundation for clarifying the complex miRNA-mediated regulatory network for growth and development. In view of this, spatio-temporal expression of miR396, miR950, miR164, miR166 and miR160 were analysed in Larix olgensis during the growth stages of not lignified, beginning of lignification, and completely lignified in different tissues (root, stem, and leaf) by quantitative real-time PCR (qRT-PCR). There were differences in the expression of miRNAs in roots, stems and leaves in the same growth period. At 60?days, miR160, miR166 and miR396-2 exhibited the highest expression in leaves. At 120?days, most miRNAs in roots and stems decreased significantly. At 180?days, miRNAs were abundantly expressed in roots and stems. Meanwhile, analysis of the expression of miRNAs in leaves revealed that miR396-2 was reduced as time went on, whereas other miRNAs increased initially and then decreased. On the other hand, in the stems, miR166-1 was increase, whereas other miRNAs, especially miR160, miR164, miR396 and miR950-1, first decreased and then increased. Similarly, in the roots, miR950-2 first decreased and then increased, whereas other miRNAs exhibited a trend of continuous increase. CONCLUSIONS:The present investigation included rapid isolation and identification of miRNAs in Larix olgensis through construction of a sRNA library using Solexa and predicted 78 novel miRNAs, which showed differential expression levels in different tissues and stages. These results provided a theoretical basis for further revealing the genetic regulation mechanism of miRNA in the growth and development of conifers and the verification of function in target genes.

Dataset Information

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

Publications

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

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