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Table 1 Perturbation signature modules from DART-CLQ predicting outcome in the endocrine-treated ER+ METABRIC set in both univariate and multivariate analysis (adjusted for grade, stage and tumor size)

From: Denoising perturbation signatures reveal an actionable AKT-signaling gene module underlying a poor clinical outcome in endocrine-treated ER+ breast cancer

 

Univariate

 

Multivariate

  
 

n =926

 

n =685

  

Module

HR (95% CI)

P *

HR (95% CI)

P *

Class

CYCLIN_D1_KE(UP)

1.14 (1.04–1.25)

0.005

1.12 (1.01–1.25)

0.039

Prolif

CSR_LATE_UP

1.19 (1.08–1.32)

0.001

1.13 (1.01–1.27)

0.039

NotTgt

AKT_UP

1.18 (1.07–1.31)

0.001

1.13 (1.01–1.27)

0.041

Tgt

PIGF_UP

0.86 (0.78–0.94)

0.001

0.88 (0.79–0.97)

0.014

HR <1

ATF2_S_UP

1.2 (1.08–1.32)

0.001

1.14 (1.01–1.28)

0.035

NotTgt

ATF2_UP

1.21 (1.09–1.34)

<0.001

1.15 (1.02–1.3)

0.019

NotTgt

E2F3_UP

1.21 (1.1–1.33)

<0.001

1.13 (1.01–1.27)

0.033

Prolif

SRC_UP

0.83 (0.75–0.91)

<0.001

0.88 (0.78–0.99)

0.036

HR <1

PRC2_EDD_UP

1.21 (1.1–1.33)

<0.001

1.15 (1.02–1.29)

0.018

NotTgt

MTOR_UP.N4

1.19 (1.08–1.32)

0.001

1.15 (1.02–1.3)

0.022

Tgt

PTEN_DN.V2

0.84 (0.76–0.94)

0.001

0.87 (0.76–0.98)

0.023

NotTgt

RB_P107_DN

1.2 (1.09–1.31)

<0.001

1.13 (1.01–1.27)

0.037

NotTgt

RB_P130_DN

1.21 (1.1–1.34)

<0.001

1.13 (1–1.27)

0.044

NotTgt

KRAS.300_UP

0.78 (0.7–0.87)

<0.001

0.79 (0.7–0.89)

<0.001

NotTgt

KRAS.600_UP

0.82 (0.74–0.92)

<0.001

0.83 (0.73–0.94)

0.004

NotTgt

KRAS.600.LUNG.BREAST_UP

0.84 (0.75–0.94)

0.003

0.84 (0.74–0.96)

0.01

NotTgt

KRAS.KIDNEY_UP

0.83 (0.75–0.92)

<0.001

0.85 (0.76–0.96)

0.008

NotTgt

  1. Hazard ratios (HRs), 95 % confidence intervals (CIs) and Cox regression P values are indicated. Perturbation activity scores were scaled to unit variance before running the Cox regression to allow meaningful comparison of HR values. Last column labels the original perturbation signatures according to whether they are targetable (Tgt, i.e., they exhibit HR >1 and there are drug inhibitors for them), not targetable (NotTgt, i.e., either no specific drug exists, or a drug does exist but the module exhibits HR <1), or if they are directly implicated in the cell cycle/proliferation (Prolif). *All P values reported in this table pass a Benjamini–Hochberg corrected FDR threshold of 0.15.