Identification of a plasma miRNA biomarker signature for allergic asthma
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Identification of a plasma miRNA biomarker signature for allergic asthma : A translational approach. / Milger, K; Götschke, J; Krause, L; Nathan, P; Alessandrini, F; Tufman, A; Fischer, R; Bartel, S; Theis, F J; Behr, J; Dehmel, S; Mueller, N S; Kneidinger, N; Krauss-Etschmann, S.
In: ALLERGY, Vol. 72, No. 12, 12.2017, p. 1962-1971.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of a plasma miRNA biomarker signature for allergic asthma
T2 - A translational approach
AU - Milger, K
AU - Götschke, J
AU - Krause, L
AU - Nathan, P
AU - Alessandrini, F
AU - Tufman, A
AU - Fischer, R
AU - Bartel, S
AU - Theis, F J
AU - Behr, J
AU - Dehmel, S
AU - Mueller, N S
AU - Kneidinger, N
AU - Krauss-Etschmann, S
N1 - © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PY - 2017/12
Y1 - 2017/12
N2 - BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach.METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls.RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use.CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.
AB - BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach.METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls.RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use.CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.
KW - Adult
KW - Aged
KW - Animals
KW - Asthma
KW - Biomarkers
KW - Circulating MicroRNA
KW - Disease Models, Animal
KW - Female
KW - Gene Expression Profiling
KW - Humans
KW - Male
KW - Mice
KW - Middle Aged
KW - ROC Curve
KW - Real-Time Polymerase Chain Reaction
KW - Reproducibility of Results
KW - Transcriptome
KW - Translational Medical Research
KW - Young Adult
KW - Journal Article
U2 - 10.1111/all.13205
DO - 10.1111/all.13205
M3 - SCORING: Journal article
C2 - 28513859
VL - 72
SP - 1962
EP - 1971
JO - ALLERGY
JF - ALLERGY
SN - 0105-4538
IS - 12
ER -