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

Oji‐Mmuo, Christiana N.; Siddaiah, Roopa; Montes, Deborah T.; Pham, Melody A; Spear, Debra; Donnelly, Ann; Fuentes, Nathalie; Imamura‐Kawasawa, Yuka; Howrylak, Judie A.; Thomas, Neal J.; Silveyra, Patricia

doi:10.1038/s41372-020-00868-9

Cited by 15 publications

(17 citation statements)

References 52 publications

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“…The exclusion criteria were as follows: (a) patients with no presumed clinical diagnosis, (b) patients with critical illnesses other than BPD, and (c) patients with incomplete RNA data, including transcriptional data of miRNA and mRNA. miRNAs that were coexpressed among the datasets, including GSE156055 [ 13 ], GSE165828 [ 14 ], and GSE108604 [ 15 ], were identified and subsequently analysed. The GSE156055 dataset includes miRNA profiles in tracheal aspirates (TAs) from 51 infants who underwent invasive mechanical ventilation.…”

Section: Methodsmentioning

confidence: 99%

Functional Analysis of Bronchopulmonary Dysplasia-Related Neuropeptides in Preterm Infants and miRNA-Based Diagnostic Model Construction

Zhang¹,

Kong

Zhang³

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Bronchopulmonary dysplasia (BPD) has a high mortality rate. This study was aimed at identifying and analysing the risk factors associated with BPD using bioinformatic and mechanical analyses and establishing a predictive model to assess the risk of BPD in preterm infants. Methods. We identified differentially expressed RNAs via the intersection of miRNAs between datasets. Online analysis tools were used to predict genes targeted by differentially expressed miRNAs (DEmiRNAs) and to generate and visualise competing endogenous RNA (ceRNA) coexpression networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed on the DEmiRNAs. In addition, an intersection analysis was performed on mRNA and neuropeptide-related genes in the ceRNA network. DEmiRNAs associated with BPD and those involved in ceRNA networks were used to establish a diagnostic prediction model. The GSE108604 dataset was used as a validation set to verify the model. Results. A total of 26 DEmiRNAs were identified from the tracheal aspirates (TAs) of patients with BPD and healthy controls. In addition, a total of 1076 DEmRNAs were obtained from the GSE8586 dataset. Functional enrichment analysis of DEmRNAs revealed an abnormal reduction in mitochondrial-related activity and cellular responses to oxidative stress in patients with BPD. The neuropeptide-related genes OPRL1 and NPPA were found to be upregulated in BPD samples. Eventually, hsa-miR-1258, hsa-miR-298, hsa-miR-483-3p, and hsa-miR-769-5p were screened out and used to establish the prediction model. Calibration curves and detrended correspondence analysis (DCA) revealed that the model had good clinical applicability. Conclusions. The prediction model provided a simple method for individualised assessment, early diagnosis, and prevention of BPD risk in preterm infants.

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Section: Methodsmentioning

confidence: 99%

Functional Analysis of Bronchopulmonary Dysplasia-Related Neuropeptides in Preterm Infants and miRNA-Based Diagnostic Model Construction

Zhang¹,

Kong

Zhang³

et al. 2022

Computational and Mathematical Methods in Medicine

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“…With this goal in mind, the aim of the present study was to analyze the expression and profile of miRNAs present in TAs obtained from a cohort of neonates with mild/moderate and severe BPD. This study was conducted as part of a larger single-center prospective cohort study with some of the results reported by us previously [15]. While our prior analysis identified miRNA signatures of prematurity and BPD pathogenesis in TAs, the current study focuses on specific miRNAs associated with BPD severity, in order to help develop more precise diagnostic markers.…”

Section: Introductionmentioning

confidence: 99%

“…In the past decade, studies have proliferated looking at different genomic, transcriptomic, epigenomic, metabolomics, and other biological biomarkers for the prediction of BPD and its severity [12][13][14][15]. To date, there are no validated biomarkers for predicting risk and disease severity in the neonatal period.…”

Section: Introductionmentioning

confidence: 99%

Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

Siddaiah¹,

Oji‐Mmuo²,

Montes³

et al. 2021

Preprint

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Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth and arrested fetal lung development. The incidence of BPD remains on the rise, as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of severe BPD. We collected tracheal aspirates (TA) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, FDR &lt; 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD vs. the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extreme premature infants contain miRNA signatures associated with severe BPD. These signatures may serve as biomarkers of disease severity in infants with BPD.

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“…In the past decade, studies have proliferated looking at different genomic, transcriptomic, epigenomic, metabolomics, and other biological biomarkers for the prediction of BPD and its severity [ 15 , 16 , 17 , 18 ]. Animal models of newborn hyperoxia have identified several pathways involved in the development of BPD, including the cyclooxygenase-2 (COX-2) [ 19 , 20 ], sirtuin-1 (SIRT1) [ 21 ], and Wnt signaling pathways [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…With this goal in mind, the aim of the present study was to analyze the expression profile of miRNAs present in TAs obtained from a cohort of neonates with mild/moderate and severe BPD. This study was conducted as part of a larger single-center prospective cohort study with some of the results reported by us previously [ 18 ]. While our prior analysis identified miRNA signatures of prematurity and BPD pathogenesis in TAs, the current study focuses on specific miRNAs associated with BPD severity, in order to help develop more precise diagnostic markers.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants

et al. 2021

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Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.

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

Cited by 15 publications

References 52 publications

Functional Analysis of Bronchopulmonary Dysplasia-Related Neuropeptides in Preterm Infants and miRNA-Based Diagnostic Model Construction

Functional Analysis of Bronchopulmonary Dysplasia-Related Neuropeptides in Preterm Infants and miRNA-Based Diagnostic Model Construction

Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants

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