Table 4 Shown are the functional validation results for 14 TFs enriched for either anthracycline drug, epirubicin (EPI) or doxorubicin (DOX) at FDR ≤0.1 and P-value ≤0.05

From: Computational discovery of transcription factors associated with drug response

Number

TF

GENMi enrichments

Cell lines

  

DOX

EPI

BTF549

MDA-MB-231

  

P-value

FDR

P-value

FDR

DOX

EPI

DOX

EPI

1

CBX3

0.0033

0.05

0.4734

0.77

  

UP

UP

2

CHD1

0.0036

0.04

0.5706

0.82

    

3

E2F6

0.0051

0.06

0.0944

0.76

    

4

ELF1

0.0008

0.05

0.3030

0.79

UP

UP

UP

UP

5

HDAC1

0.0020

0.04

0.9026

0.89

UP

UP

UP

UP

6

HMGN3

0.0077

0.05

0.4534

0.76

  

UP

UP

7

HNF4G

0.0004

0.03

0.5844

0.82

UP

UP

UP

UP

8

MYC

0.1112

0.32

0.0028

0.09

 

UP

UP

UP

9

NR2F2

0.0112

0.08

0.8199

0.82

  

UP

UP

10

POU2F2

0.0048

0.06

0.1192

0.72

  

UP

UP

11

RBBP5

0.0004

0.04

0.7434

0.83

    

12

STAT1

0.0065

0.07

0.7122

0.87

  

UP

UP

13

TEAD4

0.0101

0.07

0.8462

0.98

    

14

ZNF263

0.0071

0.05

0.1045

0.72

UP

UP

UP

UP

  1. Abbreviations: FDR, false discovery rate; GENMi, Gene Expression iN the Middle; TF, transcription factor.
  2. Validation was performed in two triple-negative breast cancer cell lines (BTF549 and MDA-MB-231). For each cell line, drug and TF, a small interfering RNA (siRNA) knockdown experiment was performed, followed by an MTA assay for the drug. Comparisons were made to negative siRNA experiments to determine whether the TF decreased, increased or did not affect the sensitivity of the cell to the drug. ‘UP’ in the table refers to decreased sensitivity or desensitization of the cell to the drug. In other words, it means that the TF knockdown increased cell resistance/survivability to increasing concentrations of the apoptotic drug. Cells with P-value ≤0.05 or FDR ≤0.1 are colored gray.