Background
Methods
Detailed methods are described within the STAR file (Additional file 1)
Patients and samples
RNA extraction
Ethics statement
Gene expression analysis and data pre-processing
Elimination of gene expression changes in the control group
Biomarker analyses
Published gene signatures
Immune or stromal score estimation
Statistical analysis
Endpoints
Results
Patient demographics and changes in Ki67
HER2-negative tumours
Predictors of de novo antiproliferative response to AI
Association of individual genes and gene signatures with change in Ki67
Gene symbol | Entrez gene name | Correlate with change in Ki67 | Correlate with residual Ki67 | ||||
---|---|---|---|---|---|---|---|
Rank by correlation coefficient (rho) | Rho | Parametric p value | Ranking by rho | Rho | Parametric p value | ||
ESR1 | NA | − 0.11 | 1.70E−01 | NA | − 0.16 | 5.30E−02 | |
Associated with good antiproliferative response | |||||||
ACADVL | Acyl-CoA dehydrogenase very long | 1 | − 0.355 | 6.90E−06 | 1 | − 0.419 | 1.00E−07 |
TRABD | TraB domain containing | 2 | − 0.333 | 2.51E−05 | 208 | − 0.241 | 2.58E−03 |
CCND1 | Cyclin D1 | 3 | − 0.328 | 3.34E−05 | 294 | − 0.226 | 4.69E−03 |
TRIP6 | Thyroid hormone receptor interactor 6 | 4 | − 0.299 | 1.71E−04 | 58 | − 0.286 | 3.18E−04 |
CTTN | Cortactin | 5 | − 0.297 | 1.88E−04 | NA | NA | > 5.00E−3 |
MRPL23 | Mitochondrial ribosomal protein L23 | 6 | − 0.295 | 2.04E−04 | 277 | − 0.228 | 4.44E−03 |
CCNI | Cyclin I | 7 | − 0.289 | 2.81E−04 | 89 | − 0.271 | 6.79E−04 |
EPHX2 | Epoxide hydrolase 2 | 7 | − 0.289 | 2.82E−04 | 8 | − 0.356 | 6.30E−06 |
IMPDH2 | Inosine monophosphate | 9 | − 0.288 | 3.00E−04 | 114 | − 0.264 | 9.45E−04 |
ARHGEF6 | Rac/Cdc42 guanine nucleotide exchange factor 6 | 10 | − 0.283 | 3.70E−04 | NA | NA | > 5.00E−3 |
ACY1 | Aminoacylase 1 | 10 | − 0.283 | 3.73E−04 | 86 | − 0.272 | 6.53E−04 |
EIF3G | Eukaryotic translation initiation factor 3 subunit G | 12 | − 0.282 | 3.91E−04 | 122 | − 0.261 | 1.08E−03 |
GLI3 | GLI family zinc finger 3 | 12 | − 0.282 | 3.97E−04 | 155 | − 0.252 | 1.59E−03 |
TTC17 | Tetratricopeptide repeat domain 17 | 14 | − 0.279 | 4.70E−04 | 6 | − 0.366 | 3.30E−06 |
SCUBE2 | Signal peptide, CUB domain and EGF-like domain containing 2 | 15 | − 0.276 | 5.24E−04 | 3 | − 0.393 | 5.00E−07 |
MRPS27 | Mitochondrial ribosomal protein S27 | 16 | − 0.274 | 5.84E−04 | 245 | − 0.236 | 3.23E−03 |
Associated with poor antiproliferative response | |||||||
PERP | PERP, TP53 apoptosis effector | 1 | 0.291 | 2.53E−04 | 161 | 0.273 | 6.09E−04 |
YWHAQ | Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta | 2 | 0.29 | 2.63E−04 | 86 | 0.328 | 3.47E−05 |
SNIP1 | Smad nuclear interacting protein 1 | 3 | 0.275 | 5.47E−04 | 210 | 0.26 | 1.15E−03 |
PNO1 | Partner of NOB1 homologue | 4 | 0.274 | 5.74E−04 | 214 | 0.258 | 1.21E−03 |
SEC22B | SEC22 homologue B, vesicle trafficking protein (gene/pseudogene) | 5 | 0.268 | 7.64E−04 | NA | NA | > 5.00E−3 |
GOLT1B | Golgi transport 1B | 5 | 0.268 | 7.92E−04 | 87 | 0.326 | 3.82E−05 |
SAP130 | Sin3A-associated protein 130 | 7 | 0.264 | 9.56E−04 | 285 | 0.24 | 2.65E−03 |
GPKOW | G-patch domain and KOW motifs | 8 | 0.261 | 1.08E−03 | 135 | 0.289 | 2.78E−04 |
NUS1 | NUS1 dehydrodolichyl diphosphate synthase subunit | 9 | 0.259 | 1.19E−03 | 187 | 0.266 | 8.67E−04 |
PLCB1 | Phospholipase C beta 1 | 10 | 0.257 | 1.28E−03 | NA | NA | > 5.00E−3 |
MBIP | MAP3K12 binding inhibitory protein 1 | 11 | 0.256 | 1.34E−03 | NA | NA | > 5.00E−3 |
VCAM1 | Vascular cell adhesion molecule 1 | 12 | 0.254 | 1.50E−03 | 132 | 0.29 | 2.62E−04 |
DNAJC8 | DnaJ heat shock protein family (Hsp40) member C8 | 13 | 0.25 | 1.79E−03 | NA | NA | > 5.00E−3 |
HENMT1 (C1orf59H) | EN methyltransferase 1 | 14 | 0.249 | 1.87E−03 | 201 | 0.261 | 1.08E−03 |
MRPL50 | Mitochondrial ribosomal protein L50 | 15 | 0.246 | 2.07E−03 | NA | NA | > 5.00E−3 |
ODF2 | Outer dense fibre of sperm tails 2 | 16 | 0.245 | 2.15E−03 | NA | NA | > 5.00E−3 |
PIGA | Phosphatidylinositol glycan anchor biosynthesis class A | 16 | 0.245 | 2.16E−03 | 209 | 0.26 | 1.13E−03 |
HDAC4 | Histone deacetylase 4 | 16 | 0.245 | 2.19E−03 | 311 | 0.236 | 3.21E−03 |
NCOA7 | Nuclear receptor coactivator 7 | 16 | 0.245 | 2.21E−03 | NA | NA | > 5.00E−3 |
Module name | Reference | Non-responders vs responders | noCCCAs vs CCCAs | ||||||
---|---|---|---|---|---|---|---|---|---|
Mean (non-responders) | Mean (responders) | t test p value | FDR | Mean (no CCCAs) | Mean (CCCAs) | t test p value | FDR | ||
ERBB2-GS.NoPAGs | Desmedt et al. | 4.901 | 4.773 | 5.01E−03 | 3.78E−02 | 4.814 | 4.798 | 6.49E−01 | 6.49E−01 |
ERBB2-GS | Desmedt et al. | 4.475 | 4.348 | 5.04E−03 | 3.78E−02 | 4.391 | 4.372 | 5.98E−01 | 6.35E−01 |
GGI-GS.NoPAGs | Sotiriou et al. | 0.683 | 0.565 | 7.83E−03 | 3.78E−02 | 0.669 | 0.476 | 7.10E−07 | 3.02E−06 |
AURKA-GS | Desmedt et al. | 2.323 | 2.217 | 1.10E−02 | 3.78E−02 | 2.311 | 2.139 | 4.82E−06 | 1.37E−05 |
IGF1-GS | Creighton et al. | -0.365 | − 0.402 | 1.62E−02 | 3.78E−02 | − 0.371 | − 0.426 | 3.95E−04 | 8.39E−04 |
Immune.2.STAT1.NoPAGs | Desmedt et al. | 7.720 | 7.526 | 1.83E−02 | 3.78E−02 | 7.608 | 7.526 | 2.27E−01 | 3.22E−01 |
STAT1-GS | Desmedt et al. | 7.819 | 7.623 | 1.84E−02 | 3.78E−02 | 7.706 | 7.623 | 2.23E−01 | 3.22E−01 |
Gene70-GS | van ‘t Veer et al. | 3.029 | 2.928 | 2.54E−02 | 3.78E−02 | 3.019 | 2.846 | 2.19E−06 | 7.45E−06 |
GDNF-GS.NoPAGs | Morandi et al. | 1.586 | 1.475 | 2.61E−02 | 3.78E−02 | 1.520 | 1.474 | 2.74E−01 | 3.58E−01 |
removedPAGs | Gao et al. | 0.555 | 0.507 | 2.65E−02 | 3.78E−02 | 0.552 | 0.467 | 7.46E−06 | 1.81E−05 |
WntTarget34-GS | VerhaeghCR2014TableS1 | 8.091 | 8.191 | 2.78E−02 | 3.78E−02 | 8.153 | 8.181 | 4.70E−01 | 5.33E−01 |
IGF1.NoPAGs | Creighton et al. | -0.603 | − 0.636 | 2.91E−02 | 3.78E−02 | − 0.608 | − 0.657 | 1.09E−03 | 2.06E−03 |
GDNF-GS | Morandi et al. | 1.699 | 1.591 | 3.08E−02 | 3.78E−02 | 1.634 | 1.594 | 3.31E−01 | 4.02E−01 |
E2Factivation-GS.NoPAGs | Miller et al. | 9.119 | 9.029 | 3.12E−02 | 3.78E−02 | 9.091 | 8.996 | 7.83E−03 | 1.33E−02 |
JClinInvest2007RBloss-GS | Bosco et al. | 7.961 | 7.802 | 3.44E−02 | 3.82E−02 | 7.960 | 7.654 | 2.83E−07 | 1.60E−06 |
GGI-GS | Sotiriou et al. | 5.364 | 5.219 | 3.59E−02 | 3.82E−02 | 5.372 | 5.068 | 1.55E−07 | 1.60E−06 |
DiLeoRBloss-GS | Malorni et al. | 7.771 | 7.600 | 4.21E−02 | 4.21E−02 | 7.781 | 7.423 | 2.29E−07 | 1.60E−06 |
Association of baseline gene expression and pre-selected signatures with 2-week residual Ki67
Association of genes and pre-selected signatures with complete cell cycle arrest
Effects of oestrogen deprivation by AI treatment on gene expression and associated pathways
Module name | HER2-negative | HER2-positive | Significance of the difference between two changes in expression (HER2−vs HER2+) | ||
---|---|---|---|---|---|
%Δ of geometric mean of intensities of a module of pre- and post-treatment | 2-sided unadjusted p value of paired t test | Geometric mean of intensities of a module of pre- and post-treatment | Unadjusted p value of paired t test | ||
ESR1 | − 23.06 | 1.54E−02 | 18.28 | 6.23E−01 | 9.18E−03 |
ERGs-GS | − 30.79 | 8.58E−14 | − 21.96 | 2.85E−03 | 5.81E−02 |
DiLeoRBloss-GS | − 27.61 | 9.81E−10 | − 30.64 | 1.41E−03 | 5.43E−01 |
JClinInvest2007RBloss-GS | − 26.11 | 5.47E−10 | − 29.45 | 1.78E−03 | 4.72E−01 |
CIN70-GS | − 25.92 | 3.26E−10 | − 28.69 | 1.81E−03 | 5.40E−01 |
E2F4activation-GS | − 25.26 | 4.54E−09 | − 30.07 | 5.02E−03 | 3.13E−01 |
GGI-GS | − 23.67 | 1.78E−09 | − 27.85 | 1.19E−03 | 3.40E−01 |
ERTarget27-GS | − 17.80 | 1.32E−15 | − 11.41 | 3.32E−02 | 1.71E−02 |
E2FmotifCellCycleAssociated-GS | − 16.75 | 5.71E−09 | − 21.72 | 2.00E−03 | 1.31E−01 |
E2Factivation-GS | − 14.45 | 2.25E−07 | − 18.20 | 1.93E−02 | 2.62E−01 |
AURKA-GS | − 13.91 | 1.08E−07 | − 15.45 | 3.94E−03 | 6.10E−01 |
Gene70-GS | − 9.37 | 1.97E−07 | − 12.34 | 6.76E−03 | 1.98E−01 |
SET-GS | − 9.34 | 1.55E−05 | − 2.08 | 5.69E−01 | 8.73E−03 |
PTEN-GS | − 7.55 | 1.44E−06 | − 8.81 | 3.62E−02 | 5.38E−01 |
ESR1.2-GS | − 5.82 | 3.01E−04 | − 0.46 | 8.49E−01 | 1.10E−02 |
ESR1.1-GS | − 5.40 | 2.99E−03 | 0.29 | 9.29E−01 | 1.50E−02 |
MYC-GS | − 4.36 | 1.98E−04 | − 3.54 | 2.24E−01 | 6.02E−01 |
IGF1-GS | − 4.15 | 4.59E−04 | − 4.07 | 7.76E−02 | 9.58E−01 |
VEGF-GS | − 3.85 | 3.33E−02 | − 0.21 | 9.48E−01 | 1.09E−01 |
GDNF-GS | − 3.41 | 1.40E−01 | − 5.23 | 4.25E−01 | 5.71E−01 |
obesity-GS | − 3.08 | 2.40E−02 | − 1.72 | 5.64E−01 | 4.55E−01 |
E2F3-GS | − 2.89 | 5.01E−05 | − 3.79 | 2.62E−02 | 3.45E−01 |
PI3K-GS | − 1.80 | 3.19E−03 | − 3.11 | 6.69E−02 | 1.23E−01 |
SRC-GS | − 1.69 | 2.83E−01 | − 1.62 | 6.46E−01 | 9.74E−01 |
AKT/mTOR-GS | − 1.62 | 4.57E−02 | − 1.95 | 3.31E−01 | 7.51E−01 |
RAS-GS | − 1.47 | 1.93E−01 | − 0.47 | 8.51E−01 | 5.04E−01 |
BetaCatenin-GS | − 1.28 | 3.83E−01 | 0.04 | 9.91E−01 | 5.07E−01 |
WntTarget34-GS | − 0.30 | 8.90E−01 | − 2.56 | 6.50E−01 | 4.28E−01 |
ERBB2-GS | 0.27 | 8.88E−01 | − 0.88 | 8.60E−01 | 6.55E−01 |
PIK3CA-GS | 0.39 | 7.20E−01 | 1.77 | 3.99E−01 | 3.42E−01 |
STAT1-GS | 0.79 | 8.27E−01 | − 7.73 | 2.98E−01 | 6.99E−02 |
CASP3-GS | 1.37 | 5.57E−01 | − 1.18 | 8.48E−01 | 3.82E−01 |
Bcell-GS | 1.71 | 6.92E−01 | − 7.38 | 3.51E−01 | 7.71E−02 |
MacTh1-GS | 2.72 | 4.94E−01 | 0.20 | 9.79E−01 | 6.38E−01 |
Tcell-GS | 2.83 | 5.38E−01 | − 6.13 | 4.73E−01 | 1.12E−01 |
Inflammatory-GS | 2.86 | 4.92E−01 | − 4.80 | 5.15E−01 | 1.55E−01 |
Immune.1-GS | 3.07 | 5.24E−01 | − 5.34 | 6.10E−01 | 1.49E−01 |
MAPK-GS | 3.21 | 6.59E−03 | 1.94 | 5.02E−01 | 4.22E−01 |
Stroma.2.PLAU-GS | 6.57 | 4.65E−02 | 4.54 | 5.14E−01 | 6.34E−01 |
Stroma.1-GS | 20.71 | 1.17E−02 | 21.87 | 1.61E−01 | 9.18E−01 |
TP53-GS | 29.90 | 6.45E−10 | 29.38 | 5.59E−03 | 9.44E−01 |
PAGs | − 4.40 | 6.44E−06 | − 6.23 | 2.06E−02 | 1.37E−01 |
Surgery gene signature scores | HER2− (n = 135) | ||||||
---|---|---|---|---|---|---|---|
Change in Ki67 (n = 121) | Residual Ki67 (n = 124) | ||||||
Signature name | Reference | Rho | p value | FDR | Rho | p value | FDR |
ESR1 | − 0.19 | 3.42E−02 | 4.62E−02 | − 0.17 | 6.53E−02 | 6.53E−02 | |
TP53-GS | Coutant et al. | − 0.47 | 7.43E−08 | 6.50E−07 | − 0.54 | 6.61E−11 | 3.57E−10 |
ERTarget27-GS | VerhaeghCR2014TableS2 | − 0.26 | 3.96E−03 | 8.22E−03 | − 0.25 | 5.25E−03 | 7.46E−03 |
SET-GS | Symmans et al. | − 0.25 | 5.38E−03 | 1.04E−02 | − 0.3 | 7.82E−04 | 1.41E−03 |
ESR1.2-GS | Desmedt et al. | − 0.24 | 8.58E−03 | 1.32E−02 | − 0.27 | 2.52E−03 | 4.00E−03 |
ESR1.1-GS | Mackay et al. | − 0.23 | 1.15E−02 | 1.63E−02 | − 0.29 | 1.34E−03 | 2.26E−03 |
ERGs-GS | Dunbier et al. | − 0.09 | 3.56E−01 | 3.70E−01 | − 0.21 | 1.96E−02 | 2.21E−02 |
PIK3CA-GS | Loi et al. | − 0.05 | 5.53E−01 | 5.53E−01 | − 0.18 | 4.07E−02 | 4.23E−02 |
MacTh1-GS | Iglesia et al. | 0.088 | 3.39E−01 | 3.66E−01 | 0.199 | 2.64E−02 | 2.85E−02 |
Inflammatory-GS | Dunbier et al. | 0.116 | 2.05E−01 | 2.31E−01 | 0.22 | 1.43E−02 | 1.68E−02 |
GDNF-GS | Morandi et al. | 0.116 | 2.04E−01 | 2.31E−01 | 0.254 | 4.40E−03 | 6.60E−03 |
obesity-GS | Creighton et al. | 0.134 | 1.43E−01 | 1.76E−01 | 0.239 | 7.61E−03 | 9.34E−03 |
Immune.2.STAT1-GS | Desmedt et al. | 0.158 | 8.26E−02 | 1.06E−01 | 0.247 | 5.64E−03 | 7.61E−03 |
E2F3-GS | Bild et al. | 0.237 | 8.79E−03 | 1.32E−02 | 0.24 | 7.38E−03 | 9.34E−03 |
IGF1-GS | Creighton et al. | 0.24 | 8.06E−03 | 1.32E−02 | 0.303 | 6.22E−04 | 1.20E−03 |
AKT/mTOR-GS | Majumder et al. | 0.249 | 5.83E−03 | 1.05E−02 | 0.362 | 3.63E−05 | 7.54E−05 |
PTEN-GS | Saale at al. | 0.286 | 1.49E−03 | 3.35E−03 | 0.392 | 6.68E−06 | 1.50E−05 |
PI3K-GS | Creighton 2010 | 0.291 | 1.21E−03 | 2.97E−03 | 0.413 | 1.92E−06 | 4.71E−06 |
AURKA-GS | Desmedt et al. | 0.32 | 3.53E−04 | 9.53E−04 | 0.427 | 7.36E−07 | 1.99E−06 |
E2Factivation-GS | Miller et al. | 0.323 | 3.08E−04 | 9.24E−04 | 0.432 | 5.39E−07 | 1.62E−06 |
E2FmotifCellCycleAssociated-GS | Miller et al. | 0.402 | 4.79E−06 | 1.62E−05 | 0.454 | 1.22E−07 | 4.12E−07 |
Gene70-GS | van ‘t Veer et al. | 0.431 | 8.22E−07 | 3.17E−06 | 0.546 | 5.64E−11 | 3.57E−10 |
CIN70-GS | Carter et al. | 0.442 | 3.89E−07 | 1.75E−06 | 0.529 | 2.79E−10 | 1.08E−09 |
E2F4activation-GS | Guerrero-Zotano et al. | 0.454 | 1.73E−07 | 9.34E−07 | 0.535 | 1.51E−10 | 6.80E−10 |
GGI-GS | Sotiriou et al. | 0.462 | 9.63E−08 | 6.50E−07 | 0.571 | 4.52E−12 | 6.10E−11 |
JClinInvest2007RBloss-GS | Bosco et al. | 0.491 | 1.12E−08 | 1.51E−07 | 0.545 | 5.89E−11 | 3.57E−10 |
DiLeoRBloss-GS | Malorni et al. | 0.526 | 5.61E−10 | 1.51E−08 | 0.584 | 1.08E−12 | 2.92E−11 |
Change in gene signature scores | HER2− (n = 135) | HER2+ (n = 22) | Significance of the difference between two correlation coefficients (HER2− vs HER2+) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Change in Ki67 (n = 121) | Residual Ki67 (n = 124) | Change in Ki67 (n = 21) | Residual Ki67 (n = 22) | ||||||||
Signature name | Reference | Rho | p value | Rho | p value | Rho | p value | Rho | p value | Change in Ki67 | Residual Ki67 |
ESR1 | − 0.08 | 3.58E−01 | 0.03 | 7.37E−01 | 0.41 | 6.70E−02 | 0.48 | 2.20E−02 | 3.69E−02 | 4.61E−02 | |
E2F4activation-GS | Guerrero-Zotano et al. | 0.38 | 2.12E−05 | 0.13 | 1.58E−01 | 0.42 | 5.84E−02 | 0.18 | 4.22E−01 | 8.47E−01 | 8.36E−01 |
DiLeoRBloss-GS | Malorni et al. | 0.36 | 4.29E−05 | 0.09 | 3.12E−01 | 0.40 | 7.55E−02 | 0.23 | 2.94E−01 | 8.50E−01 | 5.60E−01 |
JClinInvest2007RBloss-GS | Bosco et al. | 0.35 | 1.05E−04 | 0.08 | 3.87E−01 | 0.38 | 8.53E−02 | 0.22 | 3.31E−01 | 8.89E−01 | 5.62E−01 |
GGI-GS | Sotiriou et al. | 0.34 | 1.30E−04 | 0.08 | 3.75E−01 | 0.41 | 6.28E−02 | 0.24 | 2.77E−01 | 7.42E−01 | 5.05E−01 |
CIN70-GS | Carter et al. | 0.33 | 2.16E−04 | 0.09 | 3.26E−01 | 0.43 | 5.18E−02 | 0.23 | 3.04E−01 | 6.36E−01 | 5.60E−01 |
E2FmotifCellCycleAssociated-GS | Miller et al. | 0.31 | 4.37E−04 | 0.04 | 6.91E−01 | 0.53 | 1.38E−02 | 0.09 | 6.84E−01 | 2.75E−01 | 8.39E−01 |
Gene70-GS | van ‘t Veer et al. | 0.31 | 5.01E−04 | 0.05 | 5.90E−01 | 0.44 | 4.65E−02 | 0.14 | 5.46E−01 | 5.39E−01 | 7.13E−01 |
E2Factivation-GS | Miller et al. | 0.29 | 1.49E−03 | 0.13 | 1.40E−01 | 0.42 | 5.92E−02 | 0.04 | 8.59E−01 | 5.46E−01 | 7.14E−01 |
ERGs-GS | Dunbier et al. | 0.25 | 5.44E−03 | 0.28 | 1.96E−03 | 0.11 | 6.30E−01 | 0.49 | 2.07E−02 | 5.58E−01 | 3.15E−01 |
PTEN-GS | Saale at al. | 0.23 | 1.16E−02 | 0.04 | 6.24E−01 | 0.46 | 3.43E−02 | 0.20 | 3.79E−01 | 2.87E−01 | 5.10E−01 |
PI3K-GS | Creighton 2010 | 0.23 | 1.31E−02 | 0.12 | 1.95E−01 | 0.50 | 1.99E−02 | 0.37 | 9.24E−02 | 2.02E−01 | 2.79E−01 |
AURKA-GS | Desmedt et al. | 0.21 | 2.32E−02 | 0.01 | 8.70E−01 | 0.46 | 3.37E−02 | 0.38 | 7.72E−02 | 2.50E−01 | 1.15E−01 |
E2F3-GS | Bild et al. | 0.20 | 3.20E−02 | 0.07 | 4.34E−01 | 0.43 | 5.18E−02 | 0.33 | 1.36E−01 | 2.98E−01 | 2.70E−01 |
WntTarget34-GS | VerhaeghCR2014TableS1 | 0.17 | 6.11E−02 | 0.16 | 6.99E−02 | 0.11 | 6.26E−01 | − 0.09 | 6.91E−01 | 8.04E−01 | 3.09E−01 |
AKT/mTOR-GS | Majumder et al. | 0.15 | 9.44E−02 | 0.14 | 1.20E−01 | 0.29 | 2.03E−01 | 0.25 | 2.64E−01 | 5.51E−01 | 6.43E−01 |
IGF1-GS | Creighton et al. | 0.13 | 1.61E−01 | − 0.05 | 5.80E−01 | 0.32 | 1.54E−01 | 0.42 | 5.41E−02 | 4.16E−01 | 4.41E−02 |
ERTarget27-GS | VerhaeghCR2014TableS2 | 0.12 | 1.86E−01 | 0.19 | 3.26E−02 | 0.29 | 1.97E−01 | 0.41 | 5.85E−02 | 4.72E−01 | 3.25E−01 |
MacTh1-GS | Iglesia et al. | 0.10 | 2.57E−01 | 0.09 | 3.23E−01 | − 0.17 | 4.51E−01 | − 0.14 | 5.33E−01 | 2.71E−01 | 3.50E−01 |
CASP3-GS | Desmedt et al. | 0.09 | 3.06E−01 | 0.12 | 2.00E−01 | 0.17 | 4.64E−01 | − 0.08 | 7.32E−01 | 7.42E−01 | 4.17E−01 |
STAT1-GS | Desmedt et al. | 0.07 | 4.50E−01 | 0.02 | 8.06E−01 | 0.11 | 6.30E−01 | − 0.22 | 3.18E−01 | 8.70E−01 | 3.24E−01 |
GDNF-GS | Morandi et al. | 0.06 | 4.80E−01 | 0.04 | 6.99E−01 | 0.20 | 3.94E−01 | 0.03 | 8.91E−01 | 5.64E−01 | 9.68E−01 |
MYC-GS | Bild et al. | 0.06 | 5.30E−01 | − 0.10 | 2.60E−01 | 0.40 | 7.14E−02 | 0.43 | 4.41E−02 | 1.41E−01 | 2.34E−02 |
Inflammatory-GS | Dunbier et al. | 0.06 | 5.34E−01 | 0.03 | 7.56E−01 | − 0.19 | 3.97E−01 | − 0.28 | 2.04E−01 | 3.07E−01 | 1.99E−01 |
Bcell-GS | Iglesia et al. | 0.05 | 5.55E−01 | 0.02 | 7.97E−01 | − 0.01 | 9.55E−01 | − 0.54 | 9.42E−03 | 8.08E−01 | 1.16E−02 |
Tcell-GS | Iglesia et al. | 0.05 | 5.61E−01 | − 0.02 | 8.09E−01 | − 0.41 | 6.46E−02 | − 0.33 | 1.36E−01 | 4.95E−02 | 1.92E−01 |
obesity-GS | Creighton et al. | 0.05 | 5.67E−01 | − 0.12 | 1.91E−01 | − 0.22 | 3.33E−01 | 0.23 | 3.06E−01 | 2.68E−01 | 1.51E−01 |
VEGF-GS | Desmedt et al. | 0.03 | 7.41E−01 | − 0.02 | 8.34E−01 | 0.46 | 3.43E−02 | 0.63 | 1.57E−03 | 5.87E−02 | 2.07E−03 |
Stroma.2.PLAU-GS | Desmedt et al. | 0.02 | 8.14E−01 | 0.01 | 9.55E−01 | − 0.21 | 3.51E−01 | − 0.17 | 4.46E−01 | 3.46E−01 | 4.62E−01 |
BetaCatenin-GS | Bild et al. | 0.02 | 8.50E−01 | − 0.07 | 4.09E−01 | − 0.02 | 9.29E−01 | 0.33 | 1.39E−01 | 8.71E−01 | 9.48E−02 |
Stroma.1-GS | Farmer at al. | 0.00 | 9.71E−01 | 0.04 | 6.27E−01 | − 0.20 | 3.88E−01 | − 0.26 | 2.51E−01 | 4.12E−01 | 2.16E−01 |
MAPK-GS | Creighton et al. | − 0.01 | 9.24E−01 | − 0.07 | 4.24E−01 | − 0.27 | 2.36E−01 | − 0.30 | 1.70E−01 | 2.80E−01 | 3.33E−01 |
Immune.1-GS | Teschendorff at al. | − 0.01 | 9.12E−01 | − 0.03 | 7.16E−01 | − 0.16 | 4.78E−01 | 0.03 | 8.79E−01 | 5.40E−01 | 8.08E−01 |
PIK3CA-GS | Loi et al. | − 0.01 | 9.00E−01 | 0.02 | 8.03E−01 | − 0.23 | 3.22E−01 | − 0.15 | 5.13E−01 | 3.64E−01 | 4.89E−01 |
SRC-GS | Bild et al. | − 0.03 | 7.43E−01 | − 0.13 | 1.58E−01 | − 0.06 | 7.97E−01 | − 0.14 | 5.46E−01 | 9.03E−01 | 9.67E−01 |
ESR1.1-GS | Mackay et al. | − 0.05 | 6.16E−01 | 0.07 | 4.16E−01 | 0.31 | 1.71E−01 | 0.42 | 4.99E−02 | 1.34E−01 | 1.27E−01 |
SET-GS | Symmans et al | − 0.05 | 5.70E−01 | 0.09 | 3.21E−01 | 0.22 | 3.28E−01 | 0.45 | 3.36E−02 | 2.68E−01 | 1.11E−01 |
RAS-GS | Bild et al. | − 0.06 | 4.99E−01 | − 0.13 | 1.39E−01 | 0.40 | 7.44E−02 | 0.11 | 6.29E−01 | 5.04E−02 | 3.29E−01 |
ESR1.2-GS | Desmedt et al. | − 0.10 | 2.81E−01 | 0.05 | 5.69E−01 | 0.29 | 1.97E−01 | 0.62 | 2.21E−03 | 1.07E−01 | 6.32E−03 |
ERBB2-GS | Desmedt et al. | − 0.24 | 9.08E−03 | − 0.22 | 1.20E−02 | − 0.04 | 8.80E−01 | 0.15 | 5.06E−01 | 4.08E−01 | 1.29E−01 |
TP53-GS | Coutant et al. | − 0.37 | 2.38E−05 | − 0.12 | 1.82E−01 | − 0.32 | 1.63E−01 | − 0.32 | 1.43E−01 | 8.18E−01 | 3.93E−01 |
PAGs | Gao et al. | 0.27 | 3.11E−03 | 0.07 | 4.68E−01 | 0.47 | 2.99E−02 | 0.11 | 6.12E−01 | 3.45E−01 | 8.70E−01 |