Table 2.
Altered gene expression patterns after castration and vortioxetine treatment. a–c Ingenuity Pathway Analysis of changes in expression of gene networks following castration and vortioxetine treatment. d Individual genes that were altered (p<0.025) in the interaction analysis. Genes are sorted by p value in ascending order.
| Table 2a – Main Effect of Castration | ||
|---|---|---|
| Canonical Pathway | z-score | Genes |
| Superpathway of Inositol Phosphate Compounds | −3.138 | FYN, NUDT9, PPFIA3, FLT3, NUDT12, PIK3R5, PLCH2, INPP5A, KLB, CDC25B, CD28, PLCE1, IP6K1, DUSP12, PTPRN, LOC103690006, TLR9, PLD4, ITPK1, DUSP1, ITPKC, DUSP23, MTMR7, PIK3CD, PPP5C, PIP4K2C, NUDT1 |
| RANK Signaling in Osteoclasts | −2.496 | MAP3K9, FLT3, MAP3K1, PIK3R5, MAP3K4, NFKB1, TLR9, MAPK11, KLB, XIAP, FOS, PIK3CD, MAP3K2, BIRC2 |
| Adrenomedullin signaling pathway | −2.449 | FLT3, TFAP2B, PIK3R5, NOTUM, KRAS, PRKG2, NFKB1, PLCH2, MAPK11, KLB, ARNT, KCNN1, PLCE1, GPR37, PRKAR1B, PPARG, TFAP2C, ITPR2, ADCY3, TLR9, FOS, KCNQ2, PIK3CD, TNF, NPR2 |
| Role of NFAT in Cardiac Hypertrophy | −2.4 | CACNA1I, PRKCQ, ITPR2, MAP3K1, FLT3, ADCY3, NOTUM, GNB5, PIK3R5, CSNK1A1, KRAS, TLR9, PLCH2, KLB, MAPK11, CABIN1, MEF2B, CTF1, CACNG3, PLCE1, IGF1, PRKAR1B, PIK3CD, RCAN2 |
| Glioblastoma Multiforme Signaling | −2.357 | CDKN2A, WNT10B, WNT9B, AXIN1, ITPR2, FLT3, NOTUM, PIK3R5, EGF, FZD9, KRAS, TLR9, PLCH2, KLB, FZD8, PLCE1, IGF1, SMO, PIK3CD, FZD7 |
| EGF Signaling | −2.333 | FOS, ITPR2, FLT3, MAP3K1, PIK3R5, EGF, PIK3CD, TLR9, KLB, MAPK11 |
| NGF Signaling | −2.324 | MAP3K9, CREBBP, MAP3K1, FLT3, PIK3R5, CRK, KRAS, MAP3K4, TLR9, NFKB1, KLB, SMPD2, SMPD4, TRAF4, PIK3CD, RPS6KA2, MAP3K2 |
| eNOS Signaling | −2.309 | PRKCQ, FLT1, ITPR2, FLT3, ADCY3, PIK3R5, SLC7A1, AQP8, TLR9, KLB, CHRM1, HSPA2, CNGB1, PRKAR1B, VEGFD, PIK3CD, MIP, CASP8, AQP2 |
| Colorectal Cancer Metastasis Signaling | −2.294 | LRP5, WNT10B, MMP28, WNT9B, GRK2, PTGER3, AXIN1, DVL1, ADCY3, FLT3, GNB5, PIK3R5, EGF, FZD9, KRAS, TLR9, NFKB1, KLB, TLR2, FOS, FZD8, PRKAR1B, SMO, VEGFD, PIK3CD, TNF, LRP1, FZD7 |
| 3-phosphoinositide Biosynthesis | −2.236 | FYN, NUDT9, NUDT12, PPFIA3, FLT3, LOC103690006, PIK3R5, TLR9, KLB, CDC25B, CD28, ITPK1, DUSP1, DUSP23, MTMR7, PIK3CD, DUSP12, PTPRN, PPP5C, PIP4K2C, NUDT1 |
| PKCθ Signaling in T Lymphocytes | −2.183 | CACNA1I, FYN, MAP3K9, PRKCQ, HLA-A, MAP3K1, FLT3, PIK3R5, KRAS, MAP3K4, TLR9, NFKB1, CD3D, KLB, CACNG3, FOS, CD28, POU2F1, ZAP70, PIK3CD, MAP3K2 |
| Renin-Angiotensin Signaling | −2.138 | PRKCQ, ITPR2, ADCY3, FLT3, MAP3K1, REN, PIK3R5, KRAS, NFKB1, TLR9, MAPK11, KLB, FOS, PRKAR1B, PIK3CD, TNF |
| Mouse Embryonic Stem Cell Pluripotency | −2 | AXIN1, CREBBP, FLT3, DVL1, PIK3R5, FZD9, KRAS, TLR9, MAPK11, KLB, XIAP, FZD8, BMPR1A, SMO, PIK3CD, DVL3, FZD7 |
| Table 2b - Main Effect of Vortioxetine | ||
|---|---|---|
| Canonical Pathway | z-score | Genes |
| Activation of IRF by Cytosolic Pattern Recognition Receptors | 2.309 | DHX58, NFKBID, IKBKG, IRF7, JUN, NFKBIA, CREBBP, MAPK10, STAT2, IKBKE, ADAR, TNF |
| NF-κB Signaling | 2.294 | MAP3K14, FLT1, PIK3C2A, MYD88, CREBBP, MAP3K1, FLT3, FLT4, IGF2R, TAB3, NFKBID, TRADD, IKBKG, IL18, NFKBIA, BMPR1A, ZAP70, MAP3K7, PRKACA, AKT3, PIK3CD, MAP3K8, TNFRSF1B, TNF |
| Opioid Signaling Pathway | 2.117 | RGS1, RGS18, CACNA2D2, GRIN2D, SRF, AP2A2, NFKBIA, CACNG7, AKT3, RPS6KA2, PRKCA, CACNA1G, CACNB4, CREBBP, RGS16, RGS4, PPP3CC, CREB5, CALM1 (includes others), FOS, PENK, LYN, PRKACA, RGS8, RPS6KA1, MAPK7, ELK1 |
| Endothelin-1 Signaling | −2.294 | PLA2G16, PIK3C2A, ABHD3, GNA11, FLT3, PLA2G1B, CASP4, PLD4, FOS, PLA2G4E, HMOX1, CASP6, JUN, PLCE1, GNA15, LCAT, CASP2, PLA2G4B, MAPK10, CASP1, PIK3CD, ECE1, MAPK7, PLCL1, PRKC |
| Osteoarthritis Pathway | −2.263 | GLI2, FRZB, SMAD3, WNT16, CASP4, FZD1, SDC4, HES1, PGF, VEGFA, CASP6, CTNNA2, CASR, ELF3, PRG4, FGF18, BMPR1A, FOXO3, CASP1, SMO, VEGFD, TNFRSF1B, S1PR2, IL1RAPL2, DDIT4, CREBBP, COL2A1, FZD9, CEBPB, CREB5, FZD8, FZD4, CASP2, SIRT1, TNF, PPARGC1A |
| Choline Biosynthesis III | −2 | PLD4, HMOX1, CHPT1, PCYT1A |
| Table 2c - Interaction: Differential Effects of Castration in Rats Receiving Vortioxetine and Control Diet | ||
|---|---|---|
| Canonical Pathway | z-score | Genes |
| Production of Nitric Oxide and Reactive Oxygen Species in Macrophages | 3.13 | PPARA, PPP1R14C, MAP3K9, PTPN6, APOM, PRKCQ, MAP3K6, TNFRSF1A, FLT3, PLCG1, JAK2, NFKB1, SAA4, SPI1, MAPK11, FOS, RHOQ, NCF2, MAP3K8, PRKCH, CHUK, TNFRSF1B, ATM |
| Type I Diabetes Mellitus Signaling | 2.887 | MYD88, TNFRSF1A, HLA-A, SOCS6, SOCS4, JAK2, NFKB1, CD3D, MAPK11, CHUK, CASP8, TNFRSF1B, FASLG, HLA-E |
| FAT10 Cancer Signaling Pathway | 2.53 | SMAD2, MAD2L1, TNFRSF1A, ACKR3, SMAD4, CHUK, ACVR2B, NFKB1, TNFRSF1B, ACVR1C |
| TNFR1 Signaling | 2.333 | FOS, CASP6, PAK6, TNFRSF1A, PAK2, CHUK, NFKB1, CASP8, BIRC2 |
| p38 MAPK Signaling | 2.309 | MYC, RPS6KB1, TIFA, MAPKAPK3, TNFRSF1A, CREB1, PLA2G4B, RPS6KA3, IRAK3, RPS6KA2, TNFRSF1B, ELK1, MAPK11, FASLG, MEF2B |
| Salvage Pathways of Pyrimidine Ribonucleotides | 2.138 | GRK4, MAP3K9, PRKCQ, MAP3K6, SGK1, APOBEC2, UPP1, GRK5, PRKX, PAK2, PRKAA2, MAP3K8, PRKCH, MAPK7 |
| Table 2d: Genes Altered in the Interaction of Castration and Vortioxetine | |||
|---|---|---|---|
| Gene | p value | Gene | p value |
| OLR278 | 0.001740572 | RPS6KA2 | 0.017149029 |
| RGL1 | 0.002514402 | PLIN4 | 0.018137806 |
| RIN1 | 0.003228111 | FBXW10 | 0.018673401 |
| CARD9 | 0.007659412 | BPIFA5 | 0.019528063 |
| CHAT | 0.008204031 | CAPG | 0.020347608 |
| CRABP1 | 0.008388713 | ICAM2 | 0.021024904 |
| CGN | 0.009744972 | GYPC | 0.022771414 |
| DHX58 | 0.010882921 | CLGN | 0.023074521 |
| RNF19A | 0.011218841 | CALCRL | 0.023213184 |
| COLGALT2 | 0.012662084 | KLF12 | 0.02335497 |
| PIGL | 0.013260137 | CLEC16A | 0.023388837 |
| ZSWIM4 | 0.014538369 | TMEM120A | 0.023567478 |
| ABCC2 | 0.014604031 | ARL4D | 0.023629671 |
| HCRTR1 | 0.016347204 | METTL11B | 0.023760717 |
| FAM163A | 0.016641643 | IL17RE | 0.02450042 |
| ENTPD3 | 0.0169542 | SERINC2 | 0.024658007 |
| TREX2 | 0.016987793 | NPR2 | 0.024998929 |