Table 5.
Inter- versus intratumoral heterogeneity
| Protein | A | B | C | D |
|---|---|---|---|---|
| 4EBP1 | 0 | 0.1219 | 2.47 | 0.52 |
| 4EBP1p37 | 0 | 0.94719 | 2.55 | 0.47 |
| AcCoA | 0 | 0.17774 | 4.15 | 0.79 |
| AcCoAp | 0 | 0.11817 | 4.4 | 0.85 |
| Akt | 0.00029 | 0.95098 | 1.51 | 0.41 |
| Aktp308 | 0.00002 | 0.25644 | 3.57 | 0.72 |
| Aktp473 | 0.00261 | 0.35564 | 3.21 | 0.91 |
| AMPK | 0.01602 | 0.83813 | 2.28 | 0.53 |
| AMPKp | 0.00009 | 0.84344 | 2.15 | 0.56 |
| B catenin | 0 | 0.00737 | 3.18 | 0.49 |
| Bcl2 | 0 | 0.24915 | 4.46 | 0.87 |
| BRCA1 | 0.01167 | 0.74802 | 2.35 | 0.71 |
| Caveolin 1 | 0.00001 | 0.06764 | 4.99 | 1.19 |
| CCNB1 | 0 | 0.54217 | 4.72 | 0.72 |
| CCND1 | 0 | 0.88443 | 2.31 | 0.27 |
| CCNE1 | 0 | 0.07275 | 3.98 | 0.5 |
| CD31 | 0 | 0.18066 | 4.39 | 0.6 |
| CDK4 | 0 | 0.11566 | 1.75 | 0.34 |
| cjun | 0.00001 | 0.84812 | 3.0 | 0.57 |
| ckit | 0 | 0.765 | 6.32 | 1.06 |
| cleaved caspase 7 | 0 | 0.42661 | 3.73 | 0.45 |
| cleaved PARP | 0.00004 | 0.72989 | 3.64 | 0.84 |
| cmyc | 0.00006 | 0.45661 | 1.95 | 0.45 |
| Collagen.VI | 0 | 0.01389 | 6.17 | 1.2 |
| COX2 | 0.00041 | 0.1167 | 1.76 | 0.49 |
| E cadherin | 0 | 0.45206 | 2.79 | 0.53 |
| EGFR | 0 | 0.02095 | 2.87 | 0.47 |
| EGFRp1045 | 0.08967 | 0.57635 | 6.49 | 1.75 |
| EGFRp922 | 0.00011 | 0.72074 | 3.94 | 0.8 |
| ER | 0 | 0.30028 | 6.78 | 1.17 |
| ERK2 | 0.00003 | 0.69498 | 2.6 | 0.54 |
| ERp118 | 0.00001 | 0.37716 | 4.04 | 0.9 |
| ERp167 | 0.00001 | 0.09904 | 1.74 | 0.3 |
| GSK3 | 0.00002 | 0.69576 | 3.17 | 0.57 |
| GSK3p21.9 | 0.00002 | 0.25323 | 6.84 | 1.38 |
| HER2 | 0 | 0.10058 | 10.25 | 1.2 |
| HER2p1248 | 0 | 0.16499 | 7.04 | 0.77 |
| IGF1R | 0 | 0.73024 | 3.5 | 0.45 |
| IGFRp | 0.00446 | 0.28133 | 2.72 | 0.65 |
| JNK | 0.05615 | 0.99488 | 2.06 | 0.58 |
| JNKp | 0 | 0.11185 | 2.88 | 0.32 |
| MAPKp | 0 | 0.03292 | 4.38 | 0.96 |
| MEK1 | 0.00003 | 0.66118 | 1.65 | 0.42 |
| MEK12p | 0.00026 | 0.97569 | 1.21 | 0.35 |
| mTOR | 0 | 0.45838 | 2.44 | 0.33 |
| p110alpha | 0 | 0.96268 | 1.97 | 0.31 |
| p21 | 0.00007 | 0.71856 | 2.47 | 0.4 |
| p27 | 0 | 0.27306 | 2.18 | 0.28 |
| p38 | 0.00049 | 0.47474 | 1.68 | 0.39 |
| p38p180_2 | 0.00002 | 0.49019 | 2.74 | 0.63 |
| p53 | 0.00456 | 0.96661 | 5.07 | 0.95 |
| p7056 Kinase | 0.00023 | 0.24569 | 2.25 | 0.4 |
| p70S6Kp389 | 0.01012 | 0.30403 | 1.66 | 0.45 |
| PAI1 | 0.00002 | 0.75364 | 5.63 | 0.66 |
| pcmyc | 0.0041 | 0.63759 | 1.96 | 0.46 |
| PDK1 | 0 | 0.30491 | 1.5 | 0.31 |
| PDK1p241 | 0.00002 | 0.28734 | 1.64 | 0.39 |
| PKCalpha | 0 | 0.40225 | 2.58 | 0.55 |
| PKCaphap657 | 0.00001 | 0.15371 | 2.48 | 0.53 |
| pmTOR | 0.00018 | 0.50565 | 2.87 | 0.5 |
| PR | 0.00001 | 0.53572 | 6.05 | 0.88 |
| PTEN | 0.0002 | 0.04241 | 2.49 | 0.5 |
| Rab25 | 0 | 0.89192 | 2.7 | 0.45 |
| Rb | 0.00852 | 0.63485 | 2.03 | 0.63 |
| Rbp | 0.00082 | 0.0172 | 6.86 | 2.19 |
| S6 | 0 | 0.45463 | 3.9 | 0.72 |
| S6p235–236 | 0 | 0.62345 | 2.8 | 0.61 |
| S6p240_4 | 0 | 0.64948 | 3.92 | 0.71 |
| SGK | 0.00266 | 0.19466 | 2.77 | 0.86 |
| SGKp | 0.00004 | 0.80613 | 4.87 | 0.89 |
| Src | 0 | 0.90358 | 3.04 | 0.5 |
| Srcp416 | 0.00386 | 0.96558 | 4.91 | 1.01 |
| Srcp527 | 0 | 0.01943 | 1.7 | 0.39 |
| Stat3 | 0 | 0.65719 | 2.61 | 0.34 |
| Stat3p705 | 0 | 0.0244 | 2.68 | 0.42 |
| Stat3p727 | 0 | 0.75202 | 6.09 | 0.52 |
| Stat6p641 | 0.04498 | 0.44092 | 3.47 | 0.91 |
| Stathmin | 0.02785 | 0.94217 | 2.11 | 0.55 |
| TSC2 | 0 | 0.1177 | 1.81 | 0.28 |
| TSC2p | 0.00004 | 0.42417 | 1.4 | 0.25 |
| VEGFR2 | 0 | 0.05401 | 1.48 | 0.26 |
| XIAP | 0.00012 | 0.92235 | 2.68 | 0.56 |
The effects of intratumoral and intertumoral variability on breast cancer protein and phosphoprotein expression were tested by applying analysis of variance (ANOVA) models to reverse phase protein array (RPPA) data derived from ten breast tumors that were each divided into three separate pieces with assistance from a breast pathologist that were frozen immediately after surgical excision. Fold change is presented on a log2 scale. Of 82 proteins in three time 0 breast tumor replicates, the expression of 80 total and phosphoproteins demonstrated significant (ANOVA, p≤0.05) variability across the ten different breast cancers (all except EGFRp1045 and JNK), while the expression of only eight total and phosphoproteins demonstrated significant intratumoral variability within these primary breast tumors (B catenin, Collagen VI, EGFR, MAPKp, PTEN, Rbp, srcp527, stat3p705)
A ANOVA p value for intertumor variability, B ANOVA p value for intratumor variability, C maximum intertumoral fold change, D mean intratumoral fold change