Table 1 |
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|
The addition of SC236 alters expression of gene sets associated with macrophage recruitment pathways in BV-treated tumors |
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|
POSITIVELY ENRICHED GENE SETS |
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|
|
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|
NAME |
ES |
NES |
NOM p-val |
FDR q-val |
FWER p-val |
oddRatios |
|
|
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|
DNA_METABOLIC_PROCESS |
0.3612 |
1.8297 |
0.0000 |
0.0074 |
0.0134 |
1.9304 |
|
APOPTOSIS_KEGG |
0.3195 |
1.2502 |
0.1253 |
0.2551 |
0.6220 |
1.9831 |
|
SOLUBLE_FRACTION |
0.2035 |
0.9724 |
0.5341 |
0.8663 |
0.9962 |
1.5214 |
|
NEGATIVE_REGULATION_OF_PROGRAMMED_CELL_DEATH |
0.1657 |
0.7811 |
0.9662 |
0.8935 |
1.0000 |
1.2876 |
|
|
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|
NEGATIVELY ENRICHED GENE SETS |
||||||
|
|
||||||
|
NAME |
ES |
NES |
NOM p-val |
FDR q-val |
FWER p-val |
oddRatios |
|
|
||||||
|
HSA04060_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION |
-0.5365 |
-2.2777 |
0.0000 |
0.0000 |
0.0000 |
3.5618 |
|
CYTOKINE_ACTIVITY |
-0.5464 |
-2.1044 |
0.0000 |
0.0000 |
0.0000 |
3.3868 |
|
IMMUNE_RESPONSE |
-0.4609 |
-1.9351 |
0.0000 |
0.0007 |
0.0018 |
2.3685 |
|
DEFENSE_RESPONSE |
-0.4529 |
-1.9243 |
0.0000 |
0.0006 |
0.0022 |
2.2449 |
|
INFLAMMATORY_RESPONSE_PATHWAY |
-0.6176 |
-1.9127 |
0.0009 |
0.0006 |
0.0026 |
3.4287 |
|
REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS |
-0.4773 |
-1.9076 |
0.0000 |
0.0005 |
0.0026 |
2.0887 |
|
CYTOKINE_PRODUCTION |
-0.5188 |
-1.8253 |
0.0005 |
0.0017 |
0.0108 |
3.8765 |
|
HSA04514_CELL_ADHESION_MOLECULES |
-0.4568 |
-1.7974 |
0.0002 |
0.0020 |
0.0144 |
1.7020 |
|
IMMUNE_SYSTEM_PROCESS |
-0.4064 |
-1.7650 |
0.0000 |
0.0029 |
0.0230 |
1.8520 |
|
RESPONSE_TO_EXTERNAL_STIMULUS |
-0.4064 |
-1.7482 |
0.0000 |
0.0032 |
0.0286 |
2.0471 |
|
INFLAMMATORY_RESPONSE |
-0.4473 |
-1.7450 |
0.0000 |
0.0031 |
0.0300 |
2.1490 |
|
POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS |
-0.4977 |
-1.7303 |
0.0016 |
0.0035 |
0.0374 |
1.5006 |
|
RECEPTOR_BINDING |
-0.3842 |
-1.6798 |
0.0000 |
0.0058 |
0.0648 |
1.7643 |
|
RESPONSE_TO_WOUNDING |
-0.4071 |
-1.6678 |
0.0000 |
0.0064 |
0.0766 |
2.1108 |
|
IMMUNE_EFFECTOR_PROCESS |
-0.5187 |
-1.6357 |
0.0081 |
0.0082 |
0.1052 |
2.5265 |
|
LYMPHOCYTE_ACTIVATION |
-0.4637 |
-1.6207 |
0.0046 |
0.0090 |
0.1222 |
1.4574 |
|
CELL_ACTIVATION |
-0.4436 |
-1.6042 |
0.0048 |
0.0102 |
0.1460 |
1.9692 |
|
LEUKOCYTE_ACTIVATION |
-0.4516 |
-1.6008 |
0.0054 |
0.0100 |
0.1516 |
2.0518 |
|
ADAPTIVE_IMMUNE_RESPONSE_GO_0002460 |
-0.5491 |
-1.5398 |
0.0294 |
0.0181 |
0.2656 |
2.1055 |
|
ADAPTIVE_IMMUNE_RESPONSE |
-0.5268 |
-1.4882 |
0.0446 |
0.0280 |
0.3934 |
2.3657 |
|
|
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|
To assess the possibility that SC236 improves control of metastasis in the context of VEGF blockade by broadly reducing expression of inflammation-related genes, we used gene set expression analysis (GSEA) and a matrix of 67 gene sets representing pathways linked to macrophage recruitment selected from the Molecular Signatures Database (MSigDB, Broad Institute, Cambridge, MA) to explore this possibility in Affymetrix HGU133A microarray datasets from xenografts (N = 3, 4 respectively, for BV, and BV+SC236 groups). 20 gene sets were significantly negatively enriched (repressed) in combination in SC236+BV treated as compared to BV-treated tumors; no positively enriched gene set had an odds ratio > 2.0 (Table 1). Among the negatively enriched sets, we selected those with odds ratios > 3.0 in the top 5 for further analysis. Thus, it is possible that, in the context of VEGF inhibition, SC236 acts in part by limiting the ability of tumors to promote recruitment of macrophages, key elements in an inflammatory state that facilitates metastasis. |
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|
Fisher et al. Vascular Cell 2011 3:22 doi:10.1186/2045-824X-3-22 |
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