MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Population
2.2. Tracheal Aspirate Collection
2.3. MicroRNA Purification
2.4. MicroRNA Arrays
2.5. Ingenuity Pathway Analysis
2.6. MicroRNA Expression Validation
2.7. Statistical Analysis and Code Availability
3. Results
3.1. Patient Demographics
3.2. MiRNA Expression in TAs
3.3. Validation of Top Differentially Expressed miRNAs
3.4. Pathway Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | Mild/Moderate BPD (n = 8) | Severe BPD (n = 17) | p-Value |
---|---|---|---|
Gestational age (GA) at birth, weeks (mean ± SD) | 25.84 ± 2.64 | 25.39 ± 1.38 | 0.584 |
GA at sample collection, weeks (mean ± SD) | 30.75 ± 5.86 | 33.26 ± 6.02 | 0.337 |
Birth weight, grams (mean ± SD) | 704 ± 108 | 706 ± 162 | 0.981 |
Day of life (mean ± SD) | 37 ± 31 | 60 ± 40 | 0.182 |
Male sex, % (n) | 50 (4) | 47 (8) | >0.999 |
FiO2 at sample collection (mean ± SD) | 0.25 ± 0.05 | 0.35 ± 0.10 | 0.010 |
Antenatal steroids exposure, % (n) 1 | 75 (6) | 76 (13) | 0.289 |
Delivered via C-section, % (n) | 75 (6) | 88 (15) | 0.289 |
Racial/Ethnic Group, % (n) | |||
Non-Hispanic White | 63 (5) | 53 (9) | 0.508 |
Non-Hispanic Black | 25 (2) | 6 (1) | 0.289 |
Hispanic | 0 (0) | 18 (3) | 0.008 |
Asian | 13 (1) | 18 (3) | 0.070 |
More than one race | 0 (0) | 6 (1) | 0.008 |
miRNA ID | log(Fold Change) | Average Expression | FDR |
---|---|---|---|
hsa-miR-628-5p | 3.031 | 2.823 | 0.032 |
hsa-miR-185 | 1.463 | 1.591 | 0.039 |
hsa-miR-545* | 0.516 | 0.361 | 0.027 |
hsa-miR-378 | 0.479 | 0.607 | 0.044 |
hsa-miR-3713 | −0.270 | 0.152 | 0.020 |
hsa-miR-3151 | −0.404 | 0.414 | 0.027 |
hsa-miR-1295 | −0.404 | 0.495 | 0.027 |
hsa-miR-1286 | −0.488 | 0.487 | 0.047 |
hsa-miR-380 | −0.509 | 0.318 | 0.003 |
hsa-miR-15a* | −0.550 | 0.851 | 0.031 |
hsa-miR-3175 | −0.599 | 0.427 | 0.006 |
hsa-miR-493 | −0.698 | 1.030 | 0.042 |
hsa-miR-3193 | −0.759 | 0.537 | 0.008 |
hsa-miR-105* | −0.781 | 0.879 | 0.014 |
hsa-miR-4300 | −0.784 | 1.019 | 0.046 |
hsa-miR-631 | −0.815 | 0.756 | 0.034 |
hsa-miR-2116* | −0.902 | 0.954 | 0.033 |
hsa-miR-4304 | −0.951 | 0.986 | 0.019 |
hsa-miR-3125 | −0.971 | 1.316 | 0.026 |
hsa-miR-4303 | −1.046 | 1.158 | 0.011 |
hsa-miR-1908 | −1.078 | 0.960 | 0.005 |
hsa-miR-205* | −1.079 | 1.376 | 0.026 |
hsa-miR-3674 | −1.176 | 1.101 | 0.039 |
hsa-miR-615-3p | −1.243 | 1.649 | 0.047 |
hsa-miR-4305 | −1.383 | 1.613 | 0.040 |
hsa-let-7i* | −1.615 | 1.969 | 0.025 |
hsa-miR-4330 | −1.776 | 1.918 | 0.045 |
hsa-miR-1255b | −1.787 | 1.733 | 0.022 |
hsa-miR-125b-1* | −1.905 | 2.199 | 0.035 |
hsa-miR-24-1* | −2.300 | 1.153 | 0.013 |
hsa-miR-646 | −4.590 | 5.529 | 0.040 |
Top Pathways | p-Value |
---|---|
Top molecular and cellular functions | |
Cell-to-cell signaling and interaction | 9.63 × 10−4–9.63 × 10−4 |
Cellular function and maintenance | 9.63 × 10−4–9.63 × 10−4 |
DNA replication, recombination, and repair | 1.39 × 10−2–1.39 × 10−2 |
Cell death and survival | 1.86 × 10−2–1.86 × 10−2 |
Cell cycle | 2.57 × 10−2–2.57 × 10−2 |
Top diseases and disorders | |
Inflammatory disease | 2.08 × 10−5–2.08 × 10−5 |
Inflammatory response | 1.89 × 10−3–2.08 × 10−5 |
Organismal injury and abnormalities | 3.97 × 10−2–2.08 × 10−5 |
Renal and urological disease | 2.08 × 10−5–2.08 × 10−5 |
Reproductive system disease | 3.97 × 10−2–2.01 × 10−4 |
Top Associated Networks | Molecules | Score |
---|---|---|
Cell cycle, gene expression, RNA post-transcriptional modification | AGO2, miR-15a-3p, miR-9718 | 6 |
Cell-to-cell signaling and interaction, cellular assembly and organization, small molecule biochemistry | AR, LCOR, miR-615-3p, PPARG | 3 |
Cell cycle, cellular function and maintenance, cell signaling | CDC42, FOXD2, RHOA, miR-185-5p | 3 |
Cardiovascular disease, cardiovascular system development and function, cancer | CDKN2A, miR-1255b-5p | 3 |
Top Associated Networks | Score |
---|---|
Respiratory disease, cancer, organismal injury and abnormalities | 37 |
Cellular movement, immune cell trafficking, immunological disease | 35 |
Cell-to-cell signaling and interaction, cellular assembly and organization, tissue development | 33 |
Cell-to-cell signaling and interaction, cellular development, cellular growth and proliferation | 29 |
Cellular movement, hematological system development and function, immune cell trafficking | 27 |
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Siddaiah, R.; Oji-Mmuo, C.N.; Montes, D.T.; Fuentes, N.; Spear, D.; Donnelly, A.; Silveyra, P. MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants. Biomedicines 2021, 9, 257. https://doi.org/10.3390/biomedicines9030257
Siddaiah R, Oji-Mmuo CN, Montes DT, Fuentes N, Spear D, Donnelly A, Silveyra P. MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants. Biomedicines. 2021; 9(3):257. https://doi.org/10.3390/biomedicines9030257
Chicago/Turabian StyleSiddaiah, Roopa, Christiana N. Oji-Mmuo, Deborah T. Montes, Nathalie Fuentes, Debra Spear, Ann Donnelly, and Patricia Silveyra. 2021. "MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants" Biomedicines 9, no. 3: 257. https://doi.org/10.3390/biomedicines9030257