Table 2 Representative master regulators predicted to be activated or inhibited (|z-value|> 2.0) and upregulated (1.5 < z-value < 2.0) are summarized for the three WGCNA modules significant to lung SqCC (network bias-corrected p-value < 0.005), in which top annotations on canonical pathways, diseases or functions, and downstream regulatory effects are also provided.
Module ID (color) | Causal networks | Canonical pathways | Diseases or functions | Downstream regulatory effects | |||||
|---|---|---|---|---|---|---|---|---|---|
Master regulators | z-score | Top annotations (z-value) | p-value | Top annotations | p-value | (z-value) | Top annotation | Consistency | |
WM26 (blue) | MNK1/2 | 3.638 | Glucocorticoid receptor signaling | 5.01E−24 | Keratinization of epidermis | 2.46E−52 | Cell proliferation of squamous cell carcinoma cell lines | 3.795 | |
ROCK2 | 2.646 | HIPPO signaling (− 1) | 1.78E−04 | ||||||
EFNA4, EFNA3, EFNA5, EFNA2 | 2.449 | Purine ribonucleosides degradation to ribose-1-phosphate | 2.95E−04 | ||||||
EFNA1 | 2.236 | Cell cycle: G2/M DNA damage checkpoint regulation | 5.62E−04 | ||||||
Desmoplakin, DSP | 2 | ERK5 signaling | 1.74E−03 | ||||||
SFN | 2 | p53 signaling | 4.17E−03 | ||||||
Tumor protein 63 (TP63) | 1.897 | IGF-1 signaling | 4.90E−03 | ||||||
Max dimerization protein 1 (MXD1) | − 2.132 | ||||||||
KMT2D | − 2.828 | ||||||||
CDK4/6 | − 2.828 | ||||||||
WM27 (darkturquoise) | Zinc finger E-box-binding homeobox (ZEB) | 2.714 | EIF2 signaling | 1.26E−07 | Initiation of translation of protein | 9.92E−09 | N/A | ||
Carbohydrate-responsive element-binding protein (MLXIPL) | 2 | mTOR signaling | 7.59E−05 | Nonsense-mediated mRNA decay | 1.22E−07 | ||||
cdk | 2 | Regulation of eIF4 and p70S6K Signaling | 7.76E−04 | Metabolism of protein | 1.12E−05 | (− 0.436) | |||
Baculoviral IAP repeat-containing protein (BIRC5) | 1897 | Remodeling of Epithelial Adherens Junctions | 2.51E−03 | ||||||
FABP2 | 1.89 | ||||||||
MYCN | 1.633 | ||||||||
Rapamycin-insensitive companion of mTOR (RICTOR) | − 2 | ||||||||
5-Fluorouracil(5-FU), chemical drug intervention | − 2 | ||||||||
La-related protein 1 (LARP1) | − 2.24 | ||||||||
Mir200 | − 2.714 | ||||||||
WM28 (orange) | MYC | 4 | EIF2 signaling | 2.51E−35 | Initiation of translation of protein | 5.31E−39 | Cell death of osteosarcoma cells | 8.132 | |
MLXIPL | 3.873 | Regulation of eIF4 and p70S6K signaling | 2.00E−20 | Nonsense-mediated mRNA decay | 1.31E−35 | ||||
MYCN | 3.742 | mTOR signaling | 3.16E−19 | Translation of protein | 4.18E−31 | ||||
TCR | 2.449 | HIF1α signaling | 1.78E−02 | Metabolism of protein | 1.81E−21 | (− 1.72) | |||
CAMK2N2 | − 2.138 | Insulin secretion signaling pathway | 2.51E−02 | Cell death of osteosarcoma cells | 5.88E−13 | (− 2.828) | |||
CD 437, chemical drug intervention | − 2.236 | Translation of mRNA | 2.65E−11 | ||||||
ST1926, chemical drug intervention | − 2.449 | Cell death of tumor cells | 2.28E−10 | (− 2.53) | |||||
RICTOR | − 3 | Cell death of cancer cells | 1.09E−09 | (− 2.333) | |||||
Sirolimus (Rapamycin), chemical drug intervention | − 3.464 | ||||||||
La-related protein 1 (LARP1) | − 3.873 | ||||||||
