Multivariate Cox regression including the 40-gene test and breast cancer clinical variables.

<p>Total number of samples is 668. Endpoint analyzed was distant metastasis at 10 years.</p><p>Cox analysis was done stratifying by dataset.</p>1<p>HR: Hazard ratio.</p>2<p>CI: confidence interval.</p>*<p>Significant p-values.</p

Human LAd patient stratification using the mouse-derived 36-gene genomic-clinical predictor test.

<p><b>A</b>) Kaplan-Meier curves for overall survival (OS) for the pooled population of patients with lung cancer in three datasets including patients with all disease stages. Patients were stratified based on the 36-gene test as of low (green), intermediate (blue) or high (red) risk (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). <b>B</b>) Kaplan-Meier curves for early stage patients (Stages IA and IB). Patients were stratified based on the 36-gene test as of low (green), intermediate (blue) or high (red) risk. <b>C</b>) Kaplan-Meier curves for patients profiled using qRT-PCR and FFPE samples. Patients were stratified based on the 36-gene test as of low (green), or high-intermediate (red) risks (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). Owing to the small sample size, the intermediate and high risk groups were pooled. p-val: significance of survival differences (log-rank test).</p

The 682-gene signature expression pattern in mouse carcinomas is dependent on p53 expression.

<p><b>A</b>) SV40 Large-T antigen expression in mammary gland was analysed at various time-points during carcinoma formation in transgenic WAP-TNP8 mice. Heatmaps of 682-gene signature transcripts from normal mammary glands (green), primary breast carcinomas (red) and mammary samples with transgene expression at 1, 2, 3, 4 and 5 months (blue) are shown (upper panel). <b>B</b>) p53 expression was induced in lung adenomas and adenocarcinomas in the Kras^LA2/+;Trp53^LSL/LSL;Rosa26Cre^ERT2 mouse model. The heatmaps of the 682-gene signature transcripts from normal lungs (green), lung adenomas (orange) and adenocarcinomas (red) (treated and untreated) are shown (upper panel). In <b>A</b> and <b>B</b>, sample groups are ordered from left to right based on increasing Pearson correlation with the centroid template based on the 682-gene signature. Probesets are ordered from top to bottom based on T-values (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). The number of samples in each group is shown under the heatmap. The correlation values for individual samples with the centroid are shown in the middle panel. Values range from −1 (negative correlation, bluish background) to +1 (positive correlation, reddish background). The significance of the correlation for each sample is shown in the lower panel as –log₁₀(p-val). The red line indicates a p-val of 0.01.</p

Survival curves of human BC stratified using 40-gene test and depending on molecular subtypes.

<p>Kaplan-Meier curves of distant metastasis-free survival (DMFS) for patients with BC depending on ER, PR and HER2 status. Patients were stratified based on the 40-gene test as of low (green), intermediate (blue) or high (red) risk (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). p-val: significance of survival differences (log-rank test).</p

Survival curves of human LAd stratified using 36-gene genomic-clinic test and depending on molecular subtypes.

<p>Kaplan-Meier curves of overall survival for patients with LAd depending on EGFR and KRAS mutation status. Patients were stratified based on the 36-gene genomic-clinic test as of low (green), intermediate (blue) or high (red) risk (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). p-val: significance of survival differences (log-rank test).</p

The mouse skin 682-gene signature is significantly present in mouse mammary and lung carcinoma models showing p53 inhibition.

<p>Heatmaps of the 682-gene signature transcripts from (<b>A</b>) primary breast carcinomas and normal mammary glands from different transgenic GEMMs (upper panel), and from (<b>B</b>) primary and metastatic lung adenocarcinomas and normal lungs from different transgenic GEMMs (upper panel) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#pone.0042494.s011" target="_blank">Table S1</a>) are shown. The T-values returned by Student’s t-test comparisons between normal skin and carcinoma samples in which the 682-gene signature was determined (GSE11990) were used to build a centroid template. The Pearson correlation coefficient (and the corresponding p-value) with respect to the centroid was calculated for each mouse sample. Samples were ordered from left to right based on increasing correlation. Probesets are ordered from top to bottom based on T-values (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). Samples within blue rectangles are normal skin samples and skin tumour samples. The number of samples in each group is shown under the heatmaps. Pearson values are shown in the middle panel. Values range from −1 (negative correlation, bluish background) to +1 (positive correlation, reddish background). The significance value for the correlation is shown in the lower panel as –log₁₀(p-val). The red line indicates p-val = 0.01. Genotypes highlighted in red are models with p53 alterations significantly correlated with the 682-signature. Samples highlighted in pink are metastases. In (<b>B</b>), the Kras (1) and Kras/Lkb1^L/L (1) samples are from the GSE6135 dataset; the Kras (2) and Kras/Lkb1^L/L (2) samples are from the GSE21581 dataset.</p

Top 10 pertubagens identified through the Connectivity Map that induce a reverse 682-signature.

1<p>Ranking based upon permutation analysis of the same perturbagen made in the same cell line.</p>2<p>Arithmetic mean of the connectivity scores.</p>3<p>An estimate of the likelihood that the enrichment of a set of instances in the list of all instances in a given result would be observed by chance.</p

Human BC patient stratification using the mouse-derived 40-gene predictor test.

<p><b>A</b>) Kaplan-Meier curves of distant metastasis-free survival (DMFS) for a pooled population of 12 GE datasets of patients with BC. Patients were stratified based on the 40-gene test as of low (green), intermediate (blue) or high (red) risk (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). <b>B</b>) Kaplan-Meier curves of DMFS from ER+, tamoxifen-treated women with BC. Patients were stratified based on the 40-gene test as of low (green), intermediate (blue) or high (red) risk. <b>C</b>) Kaplan-Meier curves for ER+, tamoxifen-treated patients with breast cancer in the Miller dataset. Patients were stratified depending on the presence (red) or absence (green) of p53 mutations. p-val: significance of survival differences (log-rank test).</p