TABLE 4.
Pathway enrichment analysis using the transcriptional profile identified in the cardiomyocytes exposed to CA or TP at 1,000 μM individually A) or by both CA and TP B). For this analysis the Molecular Signatures Database (MSigDB v7.5.1) was utilized, and only the top enriched gene sets identified with the up-regulated or down-regulated genes (FDR <0.05, and fold change of 1.2 >) either for CA or TP, individually or by both CA and TP (common genes affected in the same directions) are shown in the tables.
| Regulated pathways by up-regulated genes by both CA and TP at 1,000 μM in cardiomyocytes | ||||||||
|---|---|---|---|---|---|---|---|---|
| Gene Set Name (# Genes (K)) | Description | # Genes in Overlap (k) | p-value | FDRq-value | ||||
| HALLMARK_TNFA_SIGNALING_VIA_NFKB (200) | Genes regulated by NF-kB in response to TNF (GeneID = 7,124) | 15 | 2.96 e-8 | 1.48 e-6 | ||||
| HALLMARK_HYPOXIA (200) | Genes up-regulated in response to low oxygen levels (hypoxia) | 12 | 7.3 e-6 | 1.83 e-4 | ||||
| HALLMARK_UV_RESPONSE_DN (144) | Genes down-regulated in response to ultraviolet (UV) radiation | 9 | 7.36 e-5 | 1.23 e-3 | ||||
| HALLMARK_MITOTIC_SPINDLE (199) | Genes important for mitotic spindle assembly | 10 | 1.82 e-4 | 1.9 e-3 | ||||
| HALLMARK_ESTROGEN_RESPONSE_EARLY (200) | Genes defining early response to estrogen | 10 | 1.9 e-4 | 1.9 e-3 | ||||
| HALLMARK_ANDROGEN_RESPONSE (101) | Genes defining response to androgens | 7 | 2.46 e-4 | 2.05 e-3 | ||||
| HALLMARK_MTORC1_SIGNALING (200) | Genes up-regulated through activation of mTORC1 complex | 9 | 8.38 e-4 | 5.24 e-3 | ||||
| HALLMARK_P53_PATHWAY (200) | Genes involved in p53 pathways and networks | 9 | 8.38 e-4 | 5.24 e-3 | ||||
| HALLMARK_HEDGEHOG_SIGNALING (36) | Genes up-regulated by activation of hedgehog signaling | 4 | 9.44 e-4 | 5.24 e-3 | ||||
| HALLMARK_PROTEIN_SECRETION (96) | Genes involved in protein secretion pathway | 6 | 1.17 e-3 | 5.85 e-3 | ||||
| HALLMARK_IL2_STAT5_SIGNALING (199) | Genes up-regulated by STAT5 in response to IL2 stimulation | 8 | 3.23 e-3 | 1.39 e-2 | ||||
| HALLMARK_KRAS_SIGNALING_UP (200) | Genes up-regulated by KRAS activation | 8 | 3.33 e-3 | 1.39 e-2 | ||||
| HALLMARK_PI3K_AKT_MTOR_SIGNALING (105) | Genes up-regulated by activation of the PI3K/AKT/mTOR pathway | 5 | 9.41 e-3 | 3.41 e-2 | ||||
| HALLMARK_ANGIOGENESIS (36) | Genes up-regulated during formation of blood vessels (angiogenesis) | 3 | 9.54 e-3 | 3.41 e-2 | ||||
| HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION (200) | Genes defining epithelial-mesenchymal transition, as in wound healing, fibrosis and metastasis | 7 | 1.18 e-2 | 3.93 e-2 | ||||
| HALLMARK_APOPTOSIS (161) | Genes mediating programmed cell death (apoptosis) by activation of caspases | 6 | 1.44 e-2 | 4.51 e-2 | ||||
| Regulated pathways by down-regulated genes by both CA and TP at 1,000 μM in cardiomyocytes | ||||||||
| Gene Set Name (# Genes K)) | Description | # Genes in Overlap k) | p -value | FDRq-value | ||||
| HALLMARK_E2F_TARGETS (200) | Genes encoding cell cycle related targets of E2F transcription factors | 4 | 2.02 e-4 | 1.01 e-2 | ||||
| HALLMARK_DNA_REPAIR (150) | Genes involved in DNA repair | 3 | 1.34 e-3 | 2.74 e-2 | ||||
| HALLMARK_APOPTOSIS (161) | Genes mediating programmed cell death (apoptosis) by activation of caspases | 3 | 1.64 e-3 | 2.74 e-2 | ||||
| HALLMARK_INTERFERON_GAMMA_RESPONSE (200) | Genes up-regulated in response to IFNG (GeneID = 3,458) | 3 | 3.04 e-3 | 3.04 e-2 | ||||
| HALLMARK_P53_PATHWAY (200) | Genes involved in p53 pathways and networks | 3 | 3.04 e-3 | 3.04 e-2 | ||||