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Multiomics endotyping of preterm infants with bronchopulmonary dysplasia and pulmonary hypertension-A pilot study
Roopa Siddaiah1, Christiana Oji-Mmuo1, Vincent P R Aluquin1
1Department of Pediatrics Penn State Health Children's Hospital Hershey Pennsylvania USA.
Insights
This study identifies specific microRNAs, transcripts, and proteins in tracheal aspirates that can help distinguish preterm infants with bronchopulmonary dysplasia and pulmonary hypertension. These biomarkers offer insights into disease mechanisms and potential endotyping.
Area of Science:
- Neonatal Medicine
- Pulmonary Medicine
- Genomics and Proteomics
Background:
- Bronchopulmonary dysplasia (BPD) is a severe complication of preterm birth, often leading to pulmonary hypertension (PH) with high mortality.
- Clinical differentiation between severe BPD with and without PH is challenging, necessitating a deeper biological understanding.
- Pulmonary hypertension associated with bronchopulmonary dysplasia (PH-BPD) requires novel biomarkers for accurate characterization and management.
Purpose of the Study:
- To identify molecular markers in tracheal aspirates for characterizing infants with PH-BPD.
- To elucidate biological processes underlying PH-BPD using multiomic analysis.
- To differentiate severe BPD with PH from severe BPD without PH through molecular signatures.
Main Methods:
- Unbiased multiomic analysis of tracheal aspirates from preterm infants with severe BPD (with and without PH).
- Utilized microRNA (miRNA) arrays, RNA sequencing, and mass spectrometry proteomics.
- Integrated analysis of miRNA, mRNA, and protein expression data.
Main Results:
- Identified 12 differentially expressed miRNAs, 6 transcripts, and 5 proteins in infants with PH-BPD compared to those with severe BPD alone.
- Pathway analysis highlighted key molecules (NFkB, VEGF, SERPINA1, IL6, ERK1/2) and affected cellular functions (development, growth, proliferation, movement).
- A comprehensive molecular signature (miRNAs, mRNAs, proteins) was established for PH-BPD.
Conclusions:
- Tracheal aspirate multiomics can provide a detailed molecular profile for endotyping infants with severe lung disease and PH.
- The identified biomarkers offer potential for improved understanding and clinical characterization of PH-BPD.
- This pilot study lays the groundwork for future diagnostic and therapeutic strategies in PH-BPD.
Abstract:
Pulmonary hypertension associated with bronchopulmonary dysplasia is a severe complication of preterm birth resulting in high mortality of up to 50% within the first 2 years of life. There is a direct relationship between bronchopulmonary dysplasia severity and incidence of associated pulmonary hypertension. However, it is challenging to clinically characterize severe bronchopulmonary dysplasia with and without pulmonary hypertension and there is need for better understanding of the two entities. Our main objective is to identify markers to help understand biological processes and characterize infants with pulmonary hypertension associated with bronchopulmonary dysplasia using tracheal aspirates. We conducted an unbiased multiomic analysis of tracheal aspirates via microRNA (miRNA) polymerase chain reaction arrays, RNA sequencing, and mass spectrometry proteomics in preterm infants with severe bronchopulmonary dysplasia with and without pulmonary hypertension (n = 46). Our pilot study analysis revealed 12 miRNAs (hsa-miR-29a, has-miR-542-3p, has-miR-624, has-miR-183, hsa-miR-501-3p, hsa-miR-101, hsa-miR-3131, hsa-miR-3683, hsa-miR-3193, hsa-miR-3672, hsa-miR-3128, and hsa-miR-1287), 6 transcripts (IL6, RPL35P5, HSD3B7, RNA5SP215, OR2A1-AS1, and RNVU1-19), and 5 proteins (CAPS, AAT, KRT5, SFTPB, and LGALS3BP) with significant differential expression in preterm infants with severe lung disease with pulmonary hypertension when compared with infants with severe lung disease but no pulmonary hypertension. Pathway analysis of the integrated multiomic expression signatures revealed NFkB, VEGF, SERPINA1, IL6, and ERK1/2 as target molecules and cellular development, cellular growth and proliferation, and cellular movement as key affected molecular functions. Our multiomic analysis of tracheal aspirates revealed a comprehensive thumbprint of miRNAs, mRNAs, and proteins that could help endotype infants with severe lung disease and pulmonary hypertension.
