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Signature of Top Omic Profile in Bronchopulmonary Dysplasia (STOP BPD)
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A7391 - Signature of Top Omic Profile in Bronchopulmonary Dysplasia (STOP BPD)
Author Block: C. V. Lal1, N. Olave2, N. Ambalavanan3; 1Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States, 2Pediatrics, University Alabama at Birmingham, Birmingham, AL, United States, 3Pediatrics, University of Alabama Birmingham, Birmingham, AL, United States.
Rationale: The overall objective of our study “STOP BPD” (Signature of Top Omic Profiles in Bronchopulmonary Dysplasia) was to prospectively define and validate clinical and “omic” signatures associated with resilience against, or risk for development of BPD, with the goal of informing the development of primary prevention strategies for BPD.
Methods: 230 extremely low birth weight (ELBW) infants were enrolled at birth. Blood/serum, tracheal aspirates and urine samples were collected within 72 hours of life. Patients were divided into four groups based on NIH BPD clinical prediction tool, and actual clinical outcomes: No BPD Concordant (Predicted to have no BPD and developed no BPD), No BPD Discordant (Predicted to have severe BPD but developed no BPD), Severe BPD Concordant (Predicted to have severe BPD, and developed severe BPD) and Severe BPD Discordant (Predicted to have no BPD, but who develop Severe BPD). In phase 1, we analyzed plasma samples collected within first 72 hours of birth for mRNA by AmpliSeq, miRNA by small RNASeq and Proteomics by Liquid chromatography-mass spectrometry (LC/MS).
Results: A very distinct serum miRNA profile differentiated Severe BPD versus No BPD. Top miRNA in severe BPD vs no BPD was hsa-miR10a-5p (Fold change 0.6, p 0.026) which has predicted targets of HIF1A, LTGB1, CXCR4, STAT5a, DNMT1, MMP3, CDH1, EYA1, ERBB2, MIF etc. Top signaling pathways affected were PDGFR alpha, aSMA, IL-11, VEGFA, Insulin/IGF1R and AR. In No BPD Discordant versus Severe BPD Discordant infants, top differentially expressed miRNA included hsa-miR10a-5p, miR-548ar-5p, miR-448g-5p, miR-449c, miR-199a, miR-30a. Predicted targets were IkBKB, JunB, DDR1, EDN1, HIF1A, SOX9, SMAD4, CD44, ERBB2, CAV1, SIRT1, TGF Beta etc. Proteomic Analysis: Serine Protease Inhibitors were reduced in severe BPD. Distinct protein network differences (such as IGF, CRP, Prdx-1 and serine peptidase inhibitors) were seen in No BPD Discordant vs. Severe BPD Discordant infants. An 'integrated' omic analysis increased the AUC of the NICHD BPD clinical predictor by 10%.
Conclusion: An integrated omic approach at birth in ELBW infants differentiates the 'predisposition to' or the 'resilience against' development of severe BPD. These findings may help in informing the development of early personalized prevention strategies for BPD in extremely preterm infants.
Author Block: C. V. Lal1, N. Olave2, N. Ambalavanan3; 1Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States, 2Pediatrics, University Alabama at Birmingham, Birmingham, AL, United States, 3Pediatrics, University of Alabama Birmingham, Birmingham, AL, United States.
Rationale: The overall objective of our study “STOP BPD” (Signature of Top Omic Profiles in Bronchopulmonary Dysplasia) was to prospectively define and validate clinical and “omic” signatures associated with resilience against, or risk for development of BPD, with the goal of informing the development of primary prevention strategies for BPD.
Methods: 230 extremely low birth weight (ELBW) infants were enrolled at birth. Blood/serum, tracheal aspirates and urine samples were collected within 72 hours of life. Patients were divided into four groups based on NIH BPD clinical prediction tool, and actual clinical outcomes: No BPD Concordant (Predicted to have no BPD and developed no BPD), No BPD Discordant (Predicted to have severe BPD but developed no BPD), Severe BPD Concordant (Predicted to have severe BPD, and developed severe BPD) and Severe BPD Discordant (Predicted to have no BPD, but who develop Severe BPD). In phase 1, we analyzed plasma samples collected within first 72 hours of birth for mRNA by AmpliSeq, miRNA by small RNASeq and Proteomics by Liquid chromatography-mass spectrometry (LC/MS).
Results: A very distinct serum miRNA profile differentiated Severe BPD versus No BPD. Top miRNA in severe BPD vs no BPD was hsa-miR10a-5p (Fold change 0.6, p 0.026) which has predicted targets of HIF1A, LTGB1, CXCR4, STAT5a, DNMT1, MMP3, CDH1, EYA1, ERBB2, MIF etc. Top signaling pathways affected were PDGFR alpha, aSMA, IL-11, VEGFA, Insulin/IGF1R and AR. In No BPD Discordant versus Severe BPD Discordant infants, top differentially expressed miRNA included hsa-miR10a-5p, miR-548ar-5p, miR-448g-5p, miR-449c, miR-199a, miR-30a. Predicted targets were IkBKB, JunB, DDR1, EDN1, HIF1A, SOX9, SMAD4, CD44, ERBB2, CAV1, SIRT1, TGF Beta etc. Proteomic Analysis: Serine Protease Inhibitors were reduced in severe BPD. Distinct protein network differences (such as IGF, CRP, Prdx-1 and serine peptidase inhibitors) were seen in No BPD Discordant vs. Severe BPD Discordant infants. An 'integrated' omic analysis increased the AUC of the NICHD BPD clinical predictor by 10%.
Conclusion: An integrated omic approach at birth in ELBW infants differentiates the 'predisposition to' or the 'resilience against' development of severe BPD. These findings may help in informing the development of early personalized prevention strategies for BPD in extremely preterm infants.
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