Table 1 Signal pathways associated with NF-κB regulons in UM-SCC cells
Tumor type* | Pathway | p53† | P-value‡ | Genes§ |
|---|---|---|---|---|
All subgroups | Ephrin receptor signaling | W | 8.1 × 10-3 | ANGPT1↓, CXCL14↓, EFNB1↓, EPHB2↑, EPHB4↓, ITGA2↓, GNA15↓, GNAI2↓, GNB1↓, GNG12↓, IL8↑, PGF↓ |
M | 2.3 × 10-3 | AKT1↓, ANGPT1↓, AXIN1↑, CXCL14↑, EFNB1↓, GNA15↓, GNAI2↓, GNB2↓, GNB4↓, GNG12↓, ITGA2↓, MAP4K4↓, PGF↓, RASA1↑, RAC2↓, RHOA↓, VEGFC↓ | ||
W+M | 8.9 × 10-4 | ANGPT1↓, AXIN1↑, CXCL14↑, EFNB1↓, EPHB2↑, GNAI2↓, GNA15↓, GNG12↓, IL8↑, ITGA2↓, PGF↓, RAC2↓, RHOA↓, VEGFC↓ | ||
Leukocyte extravasation signaling | W | 4.4 × 10-2 | CD99↓, CLDN7↑, CXCL14↓, CYBA↑, GNAI2↓, ICAM1↑, IL8↑, PRKCQ↓, TIMP2↑, VASP↓ | |
M | 1.8 × 10-3 | ACTN3↓, ACTG2↓, CD99↓, CD44↓, CLDN7↑, CXCL14↑, CYBA↑, GNAI2↓, MMP13↑, PIK3R3↑, PLCG2↑, RAC2↓, RHOA↓, TIMP2↑, VASP↓ | ||
W+M | 7.9 × 10-5 | ACTN3↓, CD99↓, CLDN7↑, CXCL14↑, CYBA↑, GNAI2↓, ICAM1↑, IL8↑, MMP13↑, PIK3R3↑, PLCG2↑, PRKCQ↓, RAC2↓, RHOA↓, TIMP2↑, VASP↓ | ||
Wnt/β-catenin signaling | W | 3.2 × 10-2 | DKK3↓, GJA1↓, PPP2R5B↓, SFRP1↓, SOX8↓, SOX9↓, TCF4↓, TGFBR2↓, TLE4↓ | |
M | 3.4 × 10-2 | AKT1↓, AXIN1↑, CCND1↑, CD44↓, DKK3↓, SOX9↓, SFRP1↓, TCF4↓, TGFB2↓, TGFBR2↓ | ||
W+M | 2.8 × 10-2 | AXIN1↑, CCND1↑, DKK3↓, PPP2R5B↓, SFRP1↓, SOX8↓, SOX9↓, TCF4↓ TGFBR2↓ | ||
Xenobiotic metabolism signaling | W | 1.2 × 10-2 | ALDH1A3↑, ALDH4A1↓, ALDH5A1↑, FMO3↓, GSTM2↓, IL1A↓, IL6↑, NOS2A↓, NQO1↑, PPARBP↓, PPP2R5B↓, PRKCQ↓, SULT1A3↑ | |
M | 8.7 × 10-3 | ALDH1A2↑, ALDH1A3↑, ALDH3B2↑, CYP1A2↑, CYP3A4↓, EIF2AK3↓, FMO3↓, IL1A↓, IL1B↓, IL6↑, NFE2L2↑, NQO1↑, PIK3R3↑, PPARBP↓, SULT1A3↑ | ||
W+M | 1.6 × 10-3 | ALDH1A2↑, ALDH5A1↑, ALDH1A3↑, ALDH3B2↑, CYP3A4↓, FMO3↓, IL1A↓, IL6↑, NOS2A↓, NQO1↑, PIK3R3↑, PPARBP↓, PPP2R5B↓, PRKCQ↓, SULT1A3↑ | ||
ERK/MAPK signaling | W+M | 4.2 × 10-2 | DUSP4↓, DUSP6↓, ELF3↑, ETS1↓, ITGA2↓, PIK3R3↑, PLCG2↑, PPP2R5B↓, PPARG↑, RAC2↓ | |
Inositol phosphate metabolism | W+M | 1.7 × 10-2 | ISYNA1↑, ITPKA↑, NEK2↑, PIK3R3↑, PIM1↑, PLK1↑, PRKCQ↓, PLCD1↓, PLCG2↑, PRKX↓ | |
IL-6 signaling | W | 4.4 × 10-2 | IKBKE↑, IL1A↓, IL1R2↓, IL1RN↓, IL6↑, IL8↑ | |
M | 1.7 × 10-2 | IL1A↓, IL1B↓, IL1R2↓, IL6↑, IL6ST↓, TNFRSF1A↓, MAP4K4↓, LBP↑ | ||
p38 MAPK signaling | W | 4.8 × 10-2 | DUSP10↑, IL1A↓, IL1R2↓, IL1RN↓, MAPKAPK3↓, TGFBR2↓ | |
M | 3.5 × 10-3 | DUSP10↑, IL1A↓, IL1B↓, IL1R2↓, MAPKAPK3↓, PLA2G4B↑, TGFB2↓, TGFBR2↓, TNFRSF1A↓ | ||
Wild-type p53-deficient | Cell cycle:G2/M DNA damage | W | 3.5 × 10-3 | CDKN1A↓, PLK1↑, RPS6KA1↓, SFN↓, TOP2A↑ |
checkpoint regulation | W+M | 1.8 × 10-2 | CDKN1A↓, PLK1↑, SFN↓, TOP2A↑ | |
Neuregulin signaling | W | 3.4 × 10-2 | ADAM17↓, ITGA2↓, NRG2↓, PDK1↑, PICK1↓, PRKCQ↓ | |
PPAR signaling | W | 3.6 × 10-2 | IL1A↓, IL1R2↓, IL1RN↓, IKBKE↑, PPARBP↓, PPARG↑ | |
Protein ubiquitination pathway | W | 3.1 × 10-2 | BIRC2↑, CDC20↑, DOC1↓, FBXW7↓, NEDD4L↓, PSMB10↑, SMURF2↓, UBE2H↓, UBE2L6↑, USP6↓ | |
Mutant p53 | GM-CSF signaling | M | 1.5 × 10-2 | AKT1↓, CCND1↑, CFS2↓, ETS1↓, PIK3R3↑, PPP3CC↓ |
W+M | 6.0 × 10-3 | CCND1↑, CFS2↓, ETS1↓, PIK3R3↑, PIM1↑, PPP3CC↓ | ||
IGF-1 signaling | M | 2.0 × 10-3 | AKT1↓, CYR61↓, IGFBP2↑, IGFBP3↑, IGFBP6↑, IRS1↑, PIK3R3↑, RASA1↑, SFN↓ | |
W+M | 3.0 × 10-2 | CYR61↓, IGFBP2↑, IGFBP3↑, IGFBP6↑, PIK3R3↑, SFN↓ | ||
Integrin signaling | M | 1.3 × 10-3 | ACTG2↓, ACTN3↓, AKT1↓, BCAR3↓, DDEF1↓, ITGA2↓, ITGA5↓, ITGB4↓, LAMA3↓, LAMB3↓, LAMC2↓, PIK3R3↑, PLCG2↑, RAC2↓, RHOA↓, RHOC↓, TSPAN4↓, TSPAN7↑, VASP↓ | |
W+M | 2.6 × 10-2 | ACTN3↓, ITGA2↓, ITGA5↓, ITGA6↓, ITGB4↓, LAMA3↓, LAMB3↓, LAMC2↓, PIK3R3↑, PLCG2↑, RAC2↓, RHOA↓, RHOC↓, VASP↓ | ||
VEGF signaling | M | 7.8 × 10-3 | ACTG2↓, ACTN3↓, AKT1↓, PGF↓, PIK3R3↑, PLCG2↑, SFN↓, VEGFC↓ | |
W+M | 3.1 × 10-2 | ACTN3↓, PGF↓, PIK3R3↑, PLCG2↑, SFN↓, VEGFC↓ | ||
NF-κB signaling | M | 1.7 × 10-2 | AKT1↓, BCL10↓, IL1A↓, IL1R2↓, IL1B↓, MALT1↓, MAP4K4↓, PIK3R3↑, PLCG2↑, TNFRSF1A↓ | |
SAPK/JNK signaling | M | 2.0 × 10-2 | DUSP4↓, DUSP10↑, EDG5↓, IRS1↑, MAP4K4↓, PIK3R3↑, RAC2↓, SH2D2A↓, ZAK↓ |