Background
Methods
Mouse osteolytic model and microarray
Analysis of gene arrays and public microarray datasets
Gene ontology (GO) and pathway analysis
Connectivity Map analysis
Results
The TA area resembles the primary tumor
TB interface-specific gene expression signature
Gene | Affymetrix probe ID | Description | Fold change | p- value | FDR p- value |
---|---|---|---|---|---|
Ibsp | 1417484_at or 1417485_at | Integrin binding sialoprotein | 7.2 | 0.05 | 0.2 |
Tnfsf11 (Rankl) | 1419083_at or 1451944_a_at | Tumor necrosis factor (ligand) superfamily, member 11 | 5.3 | 0.006 | 0.1 |
Aftph | 1426861_at | Afitiphilin | 4.8 | 0.05 | 0.2 |
Mmp13 | 1417256_at | Matrix metalloproteinase 13 | 4.7 | 0.05 | 0.2 |
Anks1b | 1447464_at | Ankyrin repeat and sterile alpha motif domain containing 1B | 4.4 | 0.02 | 0.1 |
Zic1 | 1423477_at or 1439627_at | Zinc finger protein of the cerebellum 1 | 3.7 | 0.09 | 0.2 |
Drd1a | 1455629_at or 1456051_at | Dopamine receptor 1A | 3.6 | 0.005 | 0.1 |
Alpk2 | 1452478_at | Alpha-kinase 2 | 3.2 | 0.005 | 0.1 |
Smoc2 | 1415935_at or 1431362_a_at | SPARC related modular calcium binding 2 | 3.2 | 0.01 | 0.1 |
Gene | Affymetrix probe ID | Description | Fold change | p-value | FDR p-value |
---|---|---|---|---|---|
Cnpy1 | 1437996_s_at | Canopy 1 homolog (Zebrafish) | -5.0 | 0.09 | 0.2 |
Adora3 | 1429609_at or 1430482_at | Adenosine A3 receptor | -4.7 | 0.04 | 0.2 |
Tmco5 | 1420341_at | Transmembrane and coiled-coil domains 5 | -4.5 | 0.1 | 0.2 |
V1ra2 | 1427675_at | Vomeronasal 1 receptor, A2 | -4.4 | 0.07 | 0.2 |
Maf | 1435828_at | Avian musculoaponeurotic fibrosarcoma (v-maf) AS42 oncogene homolog | -3.9 | 0.02 | 0.1 |
Dll3 | 1449236_at | Delta-like 3 | -2.9 | 0.04 | 0.2 |
Krtap16-1 | 1425655_at | Keratin associated protein 16-1 | -2.9 | 0.01 | 0.1 |
Camta1 | 1433971_at | Calmodulin binding transcription activator 1 | -3.5 | 0.01 | 0.1 |
The TB microenvironment is different than normal bone
The TB interface resembles the metastatic bone microenvironment of human breast cancer
The TB interface resembles osteoclastogenesis in culture
Pathways associated with the TB interface
GO ID | Alias | BH | p-value | Statistic |
---|---|---|---|---|
GO:0007219 | Notch signaling pathway | 0.001 | 2.65e-05 | 78.7 |
GO:0007155 | Cell adhesion | 0.001 | 3.39e-06 | 56.3 |
GO:0022610 | Biological adhesion | 0.001 | 3.39e-06 | 56.3 |
GO:0007178 | Transmembrane receptor protein serine/threonine kinase signaling pathway | 0.001 | 3.63e-06 | 77.0 |
GO:0007249 | I-kappaB kinase/NF-kappaB cascade | 0.001 | 4.49e-05 | 93.6 |
GO:0005164 | Tumor necrosis factor receptor binding | 0.001 | 4.49e-05 | 93.6 |
GO:0002761 | Regulation of myeloid leukocyte differentiation | 0.005 | 0.00052 | 96.3 |
GO:0045637 | Regulation of myeloid cell differentiation | 0.005 | 0.00052 | 96.3 |
GO:0007179 | Transforming growth factor beta receptor signaling pathway | 0.008 | 0.0014 | 93.5 |
GO:0017015 | Regulation of transforming growth factor beta receptor signaling pathway | 0.008 | 0.0014 | 93.5 |
KEGG ID | Alias | p-value | BH | Statistic |
---|---|---|---|---|
04060 | Cytokine-cytokine receptor interaction | 7.60e-05 | 0.003 | 75.3 |
01100 | Metabolic pathways | 8.88e-05 | 0.003 | 52.8 |
05016 | Huntington's disease | 9.74e-05 | 0.003 | 57.9 |
04310 | Wnt signaling pathway | 1.07e-04 | 0.003 | 72.0 |
00061 | Fatty acid biosynthesis | 1.26e-04 | 0.003 | 98.2 |
04912 | GnRH signaling pathway | 1.26e-04 | 0.003 | 57.6 |
04020 | Calcium signaling pathway | 3.59e-04 | 0.007 | 67.1 |
05010 | Alzheimer's disease | 4.15e-04 | 0.007 | 66.5 |
04650 | Natural killer cell mediated cytotoxicity | 5.35e-04 | 0.008 | 60.9 |
04012 | ErbB signaling pathway | 6.28e-04 | 0.009 | 59.9 |
Alias | p-value | BH | Statistic |
---|---|---|---|
INTRINSICPATHWAY | 0.0004 | 0.0007 | 96.9 |
BLOOD_CLOTTING_CASCADE | 0.0004 | 0.0007 | 96.9 |
HSIAO_LIVER_SPECIES_GENES | 0.0004 | 0.0007 | 96.9 |
TPA_SENS_MIDDLE_DN | 0.0004 | 0.0007 | 96.9 |
TPA__SENS_LATE_DN | 0.0004 | 0.0007 | 96.9 |
TPA__SENS_EARLY_DN | 0.0004 | 0.0007 | 96.9 |
HSA04610_COMPLEMENT_AND_COAGULATION_CASCADES | 0.0004 | 0.0007 | 96.9 |
BROWN_MYELOID_PROLIF_AND_SELF_RENEWAL | 0.0062 | 0.010 | 60.2 |
BROWN_GRAN_MONO_DIFFERENTIATION | 0.0121 | 0.017 | 38.9 |
KAMMINGA_EZH2_TARGETS | 0.0521 | 0.068 | 65.2 |