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Table 3 Upstream regulators of metronomic CPA-responsive human 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 (human gene targets)
IFNL1/IL29 Cytokine 1.72E-29 36
IFNG Cytokine 5.04E-23 68
IFNA2 Cytokine 8.87E-23 36
TGM2 Enzyme 6.30E-14 43
IFNB1 Cytokine 7.98E-10 14
Interferon alpha Cytokine 1.57E-07 23
PAF1 Transcription complex 1.89E-07 14
IRF1 Transcription regulator 1.25E-06 12
IL27 Cytokine 1.65E-06 14
Growth hormone Protein hormone 1.37E-05 12
COL18A1 Endostatin precursor 9.08E-05 13
B. Inhibited upstream regulators (human gene targets)
MAPK1 Kinase 4.88E-30 57
IL1RN Cytokine 2.26E-15 26
HIF1A Transcription regulator 1.09E-14 40
EPAS1 Transcription regulator 6.48E-12 24
NUPR1 Transcription regulator 3.60E-11 68
GAPDH Enzyme 2.75E-10 14
NEDD9 Cell adhesion protein 2.34E-08 13
SOCS1 Cytokine signaling inhibitor 6.93E-08 12
MAP3K7/TAK1 Kinase 1.05E-07 12
ERK1/2 Kinase 1.47E-07 22
RELA Transcription regulator 4.72E-07 24
TGFB1 Growth factor 6.69E-06 37
  1. Regulators were identified by IPA of the set of U251 human tumor cell genes up-regulated or down-regulated by metronomic CPA in common at both the day 12 and day 18 times points. Shown are the upstream regulators whose activation state is reliably predicated to be activated (A) or inhibited (B) by CPA treatment, based on a bias-corrected |Z-score| >2, and that meet the stringent threshold for overlap with the target gene set at p < E-04 and contain a minimum of 10 target genes in the regulated gene set. 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 S3.