Tracheal aspirate transcriptomic and miRNA signatures of extreme premature birth with bronchopulmonary dysplasia

Abstract

Objective

Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with prematurity and BPD.

Study design

We analyzed miRNA and mRNA profiles in tracheal aspirates (TAs) from 55 infants receiving invasive mechanical ventilation. Twenty-eight infants were extremely preterm and diagnosed with BPD, and 27 were term babies receiving invasive mechanical ventilation for elective procedures.

Result

We found 22 miRNAs and 33 genes differentially expressed (FDR < 0.05) in TAs of extreme preterm infants with BPD vs. term babies without BPD. Pathway analysis showed associations with inflammatory response, cellular growth/proliferation, and tissue development.

Conclusions

Specific mRNA-miRNA signatures in TAs may serve as biomarkers for BPD pathogenesis, a consequence of extreme prematurity.

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Fig. 1: MiRNA expression in newborn tracheal aspirates.
Fig. 2: Gene expression in newborn tracheal aspirates.
Fig. 3: Network analysis of differentiallly expressed genes and miRNAs.

Code availability

The code used for data analysis in the current study can be found in the Silveyra lab repository, available at http://psilveyra.github.io/silveyralab/.

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Acknowledgements

The authors thank Susan DiAngelo for assistance with sample and data collection. The authors thank the Pennsylvania State University College of Medicine Genome Sciences Core Facility for RNAseq analysis and Real Time PCR equipment.

Funding

This work was supported by grants from Children’s Miracle Network (PS, CNO), Center for Research for Women and Newborn Health (PS, NF, RS), and Penn State College of Medicine faculty endowment funds (CNO, PS, RS).

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Contributions

CNO participated in design of work, acquired samples, analyzed and interpreted data, drafted the work, and revised the work; RS participated in design of work, acquired samples, analyzed data, interpreted work, drafted the work, and revised the work; DTM purified samples, conducted validation studies, analyzed data, interpreted work, drafted the work, prepared figures, and revised the work; MAP purified and annotated samples, obtained array data, analyzed the work, and revised the work; DS acquired samples, obtained data, and revised the work; AD acquired samples, obtained data, and revised the work; NF conducted pathway analysis, created tables, and revised the work; YIK conducted RNA sequencing experiments and revised the work, JAH participated in design of work, and revised the work, NJT participated in design of work, and revised the work; PS led all stages of work from initial conceptualization, study design, data generation, transcriptomics, bioinformatics analysis and interpretation, and manuscript generation and revision.

Corresponding author

Correspondence to Patricia Silveyra.

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Oji-Mmuo, C.N., Siddaiah, R., Montes, D.T. et al. Tracheal aspirate transcriptomic and miRNA signatures of extreme premature birth with bronchopulmonary dysplasia. J Perinatol (2020). https://doi.org/10.1038/s41372-020-00868-9

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