Table 4.
Upstream Mediators Predicted to Have a Changed Activity in COPD HBEC on COPD Bronchial Scaffolds Compared with Normal Bronchial Scaffolds after 7 Days of Differentiation, Based on the Expression Pattern of Differentially Expressed Genes
| Upstream Mediator | Predicted Activity | Activation Z-Score | P Value |
|---|---|---|---|
| MYC | Increased | 7.8 | 4.4 × 10−34 |
| MYCN | Increased | 7.3 | 1.3 × 10−25 |
| ESR1 | Increased | 6.4 | 5.1 × 10−27 |
| RABL6 | Increased | 5.8 | 2.0 × 10−26 |
| E2F family | Increased | 4.3 | 1.8 × 10−26 |
| β-Estradiol | Increased | 4.1 | 4.5 × 10−32 |
| HGF | Increased | 3.9 | 1.1 × 10−32 |
| E2F1 | Increased | 3.8 | 2.3 × 10−28 |
| VEGF family | Increased | 3.7 | 3.0 × 10−25 |
| E2F3 | Increased | 3.4 | 3.8 × 10−26 |
| ERBB2 | Increased | 2.6 | 1.0 × 10−56 |
| FOXO3 | Decreased | −2.3 | 5.4 × 10−23 |
| CDKN1A | Decreased | −3.2 | 1.8 × 10−40 |
| RB1 | Decreased | −3.8 | 1.9 × 10−28 |
| MIRLET7I | Decreased | −4.6 | 1.9 × 10−27 |
| CDKN2A | Decreased | −5.8 | 3.0 × 10−32 |
| TP53 | Decreased | −6.0 | 1.3 × 10−68 |
| TNFα | Decreased | −6.3 | 1.0 × 10−25 |
| NUPR1 | Decreased | −7.2 | 5.2 × 10−29 |
| TGFB1 | Decreased | −8.1 | 5.8 × 10−46 |
Definition of abbreviations: CDKN1A = cyclin-dependent kinase inhibitor 1A (p21); CDKN2A = cyclin-dependent kinase inhibitor 2A (p16-INK4A/p14-ARF); COPD = chronic obstructive pulmonary disease; ERBB2 = Erb-b2 receptor tyrosine kinase 2; ESR1 = estrogen receptor 1; FOXO3 = forkhead box O3; HBEC = human bronchial epithelial cells; HGF = hepatocyte growth factor; MIRLET7I = microRNA let-7i (let-7); MYC = MYC protooncogene, bHLH transcription factor; MYCN = MYCN protooncogene, bHLH transcription factor; NUPR1 = nuclear protein 1, transcriptional regulator; RABL6 = RAB, member RAS oncogene family–like 6; RB1 = retinoblastoma protein transcriptional corepressor 1; TGFB1 = transforming growth factor β1; TP53 = tumor protein p53; VEGF = vascular endothelial growth factor.
Positive and negative activation z-scores indicate increased and decreased activity, respectively, on COPD scaffolds compared with normal scaffolds. The analysis was performed by using Ingenuity Pathway Analysis. Shown are the 20 upstream mediators with the lowest P values sorted by the activation z-score.