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Table 5 Upstream regulators of metronomic CPA-responsive mouse genes

From: Transcriptional profiling provides insights into metronomic cyclophosphamide-activated, innate immune-dependent regression of brain tumor xenografts

Upstream regulator Molecule type p-value of overlap # of target genes
A. Activated upstream regulators (mouse gene targets)
IFNAR Interferon receptor 5.34E-14 31
IRF3 Transcription regulator 5.62E-12 28
IFNG Interferon 2.55E-11 80
IL12 (complex) Cytokine 1.04E-10 24
STAT1 Transcription regulator 1.32E-10 37
IRF7 Transcription regulator 1.64E-10 23
IFN alpha/beta Interferon 3.98E-09 20
NFATC2 Transcription regulator 4.77E-09 26
IFNB1 Cytokine 9.37E-09 34
TLR4 Toll-like receptor 3.19E-08 42
DOCK8 other 4.22E-08 21
SASH1 other 7.34E-08 21
TICAM1 Adapter for TLR3 1.05E-07 28
ITK Kinase 1.52E-07 22
SAMSN1 other 2.20E-07 23
mir-223 MicroRNA 3.67E-07 24
DDX58 Enzyme 1.15E-06 14
IL6 Interleukin 6 1.22E-06 30
SPI1 Transcription regulator 1.31E-06 19
IKBKB Kinase that activates REL/NF B 3.41E-06 31
NOS2 Nitric oxide synthase; M1 macrophage marker 3.83E-06 30
MYD88 Adapter for TLRs 7.34E-06 32
TLR3 Transmembrane receptor 8.10E-06 27
BNIP3L Pro-apoptotic factor 9.69E-06 15
TLR9 Transmembrane receptor 1.33E-05 25
NLRP3 Inflammasome 1.59E-05 15
IRF5 Transcription regulator 2.22E-05 12
PPARG Ligand-dependent nuclear receptor 5.21E-05 40
IL18 Cytokine 6.86E-05 11
FADD Transmembrane receptor adapter protein 7.33E-05 15
CD44 Enzyme 7.53E-05 22
CDKN2A Transcription regulator 8.10E-05 20
B. Inhibited upstream regulators (mouse gene targets)
CSF2/GM-CSF Cytokine 3.82E-15 45
TRIM24 Transcription regulator 8.10E-13 32
PTGER2 G-protein coupled receptor 1.65E-09 26
DNASE2 Enzyme 4.26E-08 14
ACKR2 G-protein coupled receptor 4.87E-08 15
SOCS1 other 1.26E-07 20
mir-21 MicroRNA 1.67E-06 25
TGFB1 Growth factor 9.61E-06 19
MYC Transcription regulator 1.46E-05 24
  1. Upstream regulators were identified by IPA analysis of the set of mouse genes up-regulated or down-regulated by metronomic CPA in common in U251 tumors after three metronomic CPA treatments (day 18) and in 9L tumors after four metronomic CPA treatments (day 24), as described in Methods. Shown are the upstream regulators whose activation state is reliably predicated to be activated (A) or inhibited (B) by CPA treatment, with other details as described in TableĀ 3. More complete information, including Z-scores, lists of target genes for each regulator, associated mechanistic networks, and other upstream regulators are shown in Additional file 1: Table S7.