Table 1 RS-35d DEPs common to RAD51, ATM, ATR and DNA-PK interactomes.

From: Investigating synthetic lethality and PARP inhibitor resistance in pancreatic cancer through enantiomer differential activity

Protein

Gene

log2 (FC)

−log (p-value)

Pathway/role in PDAC

 

Ref.

CEBPB

CEBPB

1.29

1.85

Transcription factor involved in inflammatory responses; Tumour suppressor in PDAC

 

[93, 94]

NPM

NPM1

1.07

5.96

Involved in genomic stability; Promoter of aerobic glycolysis and cell cycle regulator in PDAC

 

[95,96,97]

SQSTM

SQSTM1

1.20

4.15

Autophagy and oxidative stress regulator also in PDAC

 

[98]

TCTP

TPT1

1.56

1.34

DNA damage-responsive and involved in PDAC cell growth and progression

 

[99, 100]

AP1B1

AP1B1

−1.71

3.00

Controls cGAS/STING pathway termination

 

[101]

ARID2

ARID2

−1.91

1.64

Major component of the SWI/SNF chromatin-remodelling complex

 

[102]

ATRX

ATRX

−1.88

1.49

Chromatin-remodelling factor linked to KRAS-mediated PDAC promotion

 

[103]

BRE1A

RNF20

−2.10

1.91

Promotes chromosome segregation and HR as part of RPA/RNF20/SNF2H cascade

 

[104]

CDC73

CDC73

−1.03

1.42

Associated with PDAC patients with the germline pathogenic variant CDKN2A+

 

[105]

CUL3

CUL3

−1.44

1.57

Promotes tumour growth as part of the KEAP1/Nrf2/CUL3 axis

 

[106]

DCAF1

DCAF1

−1.83

1.34

Linked with cell cycle, cell growth, cell division, cell survival and tumorigenesis in PDAC

 

[107]

DPOD1

POLD1

−2.90

1.34

3′-exonuclease domain-containing DNA polymerase linked with genome stability

 

[108]

ERCC2

ERCC2

−2.26

2.10

NER mediator required for DNA unwinding; linked to gemcitabine/CDDP polychemotherapy resistance

 

[109]

FACD2

FANCD2

−3.45

2.51

HR efficiency-related; Pro-tumorigenic role; linked to platinum sensitivity/resistance also in PDAC

 

[13, 110, 111]

FANCI

FANCI

−1.76

2.07

HR efficiency-related; linked to platinum sensitivity/resistance also in PDAC

 

[13, 110]

HUS1

HUS1

−1.77

1.53

Part of the 9-1-1 DNA checkpoint clamp involved in DNA DSBs repair; proposed synergism with PARGi in PDAC

 

[112, 113]

KEAP1

KEAP1

−1.20

2.53

Promotes tumour growth as part of the KEAP1/Nrf2/CUL3 axis

 

[106, 114]

NMRL1

NMRAL1

−2.47

1.85

Prevents apoptosis in PDAC

 

[115]

RFA3

RPA3

−3.53

1.41

HR efficiency-related; necessary for replication in various cell types

 

[13, 116]

TE2IP

TERF2IP

−3.34

1.74

Part of a prognostic signature of 15 inflammation-related gene markers in PDAC

 

[117]

TEAD1

TEAD1

−3.79

1.52

Associated with PDAC progression

 

[118, 119]

TELO2

TELO2

−1.23

2.10

Regulator of mTOR activity

 

[120]

TTI1

TTI1

−2.30

1.41

TELO2 regulator; takes part in mTOR regulation

 

[121]

UHRF2

UHRF2

−2.15

2.02

Pro-growth effect; overexpression linked with lower DFS and OS in CRC patients

 

[122]

  1. AP1B1 adaptor related protein complex 1 subunit beta 1, ARID2 AT-rich interactive domain-containing protein 2, ATRX ATRX chromatin remodeler, BRE1A RING-type E3 ubiquitin transferase BRE1A, CDC73 cell division cycle 73, CEBPB CCAAT/enhancer-binding protein beta, CRC colorectal cancer, CUL3 cullin 3, CDKN2A cyclin-dependent kinase inhibitor 2A, DCAF1 DDB1 and CUL4 associated factor 1, DFS disease-free survival, DPOD1 DNA polymerase delta catalytic subunit, ERCC2 ERCC excision repair 2, TFIIH core complex helicase subunit, FACD2 Fanconi anaemia complementation group D2, FANCI Fanconi anaemia complementation group I, FC fold change, HUS1 HUS1 checkpoint clamp component, KEAP1 Kelch-like ECH-associated protein 1, KRAS Kirsten rat sarcoma virus, mTOR mammalian target of rapamycin, NER nucleotide excision repair, NMRL1 NmrA like redox sensor 1, NPM nucleophosmin, Nrf2 nuclear factor erythroid 2-related factor 2, OS overall survival, PARGi poly (ADP-ribose) glycohydrolase (PARG) inhibitor, RFA3 replication factor A protein 3, SQSTM sequestosome 1, SWI/SNF switch/sucrose non-fermentable, TCTP translationally controlled tumour protein, TE2IP telomeric repeat-binding factor 2-interacting protein 1, TEAD1 TEA domain transcription factor 1, TELO2 telomere length regulation protein TEL2 homologue, TTI1 TELO2 interacting protein 1, UHRF2 ubiquitin like with PHD and ring finger domains 2.
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