Werner Syndrome protein expression in breast cancer
Werner Syndrome protein expression in breast cancer
Introduction
Werner protein (WRN) plays an important role in DNA repair, replication, transcription, and consequently genomic stability via its DNA-helicase and exonuclease activity. Loss of function of WRN is associated with Werner syndrome (WS), which is characterized by premature aging and cancer predisposition. Malignancies that are commonly linked to WS are thyroid carcinoma, melanoma, breast cancer, meningioma, and soft tissue and bone sarcomas. Currently, the clinicopathologic significance of WRN in breast cancer is largely unknown.
Patients and Methods
We investigated the clinicopathologic and prognostic significance of WRN protein expression in a cohort of clinically annotated series of sporadic (n = 1650) and BRCA-mutated (n = 75) invasive breast cancers. We correlated WRN protein expression to clinicopathologic characteristics, DNA repair protein expression, and survival outcomes.
Results
There is strong evidence of association between low nuclear and cytoplasmic WRN co-expression and low levels of KU70/KU80, DNA-PK, DNA Pol-B, CKD18, cytoplasmic RECQL4, and nuclear BLM protein expression (adjusted P-values <.05). Tumors with low nuclear or cytoplasmic WRN expression have worse overall breast cancer-specific survival (BCSS) (adjusted P-values <.05). In topoisomerase I overexpressed tumors, low WRN nuclear expression was associated with poor BCSS (P-value <.05). In BRCA-mutated tumors, low WRN cytoplasmic expression conferred shortest BCSS (P <.05).
Conclusions
Low WRN protein expression is associated with poor BCSS in patients with breast cancer. This can be used to optimize the risk stratification for personalized treatment.
Biomarker, Breast Cancer, Helicase, WRN, Werner Syndrome Protein
Savva, Constantinos
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Sadiq, Maaz
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Sheikh, Omar
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Karim, Syed
b809de66-3c16-44cf-8b1c-fd156b61f4a7
Trivedi, Sachin
660ebe7b-bf43-4747-8285-996bc89b3f99
Green, Andrew R.
e6f2c52e-c140-42da-af35-0ff10cf05978
Rakha, Emad A.
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Madhusudan, Srinivasan
b09d6e47-8c8f-484f-83cf-e77c2de21952
Arora, Arvind
f557b663-05bf-40ad-951b-9533cd84c403
Savva, Constantinos
d6e87674-1443-41f4-84ba-81c1ccfeb3d7
Sadiq, Maaz
f1e78d48-e202-44ce-ae0f-52ac33c70ce1
Sheikh, Omar
0a00df25-5665-49d4-ac2b-456c2ec7bc4e
Karim, Syed
b809de66-3c16-44cf-8b1c-fd156b61f4a7
Trivedi, Sachin
660ebe7b-bf43-4747-8285-996bc89b3f99
Green, Andrew R.
e6f2c52e-c140-42da-af35-0ff10cf05978
Rakha, Emad A.
26d9b09b-90c9-4e04-87ae-d95135d76a2b
Madhusudan, Srinivasan
b09d6e47-8c8f-484f-83cf-e77c2de21952
Arora, Arvind
f557b663-05bf-40ad-951b-9533cd84c403
Savva, Constantinos, Sadiq, Maaz, Sheikh, Omar, Karim, Syed, Trivedi, Sachin, Green, Andrew R., Rakha, Emad A., Madhusudan, Srinivasan and Arora, Arvind
(2020)
Werner Syndrome protein expression in breast cancer.
Clinical Breast Cancer.
(doi:10.1016/j.clbc.2020.07.013).
Abstract
Introduction
Werner protein (WRN) plays an important role in DNA repair, replication, transcription, and consequently genomic stability via its DNA-helicase and exonuclease activity. Loss of function of WRN is associated with Werner syndrome (WS), which is characterized by premature aging and cancer predisposition. Malignancies that are commonly linked to WS are thyroid carcinoma, melanoma, breast cancer, meningioma, and soft tissue and bone sarcomas. Currently, the clinicopathologic significance of WRN in breast cancer is largely unknown.
Patients and Methods
We investigated the clinicopathologic and prognostic significance of WRN protein expression in a cohort of clinically annotated series of sporadic (n = 1650) and BRCA-mutated (n = 75) invasive breast cancers. We correlated WRN protein expression to clinicopathologic characteristics, DNA repair protein expression, and survival outcomes.
Results
There is strong evidence of association between low nuclear and cytoplasmic WRN co-expression and low levels of KU70/KU80, DNA-PK, DNA Pol-B, CKD18, cytoplasmic RECQL4, and nuclear BLM protein expression (adjusted P-values <.05). Tumors with low nuclear or cytoplasmic WRN expression have worse overall breast cancer-specific survival (BCSS) (adjusted P-values <.05). In topoisomerase I overexpressed tumors, low WRN nuclear expression was associated with poor BCSS (P-value <.05). In BRCA-mutated tumors, low WRN cytoplasmic expression conferred shortest BCSS (P <.05).
Conclusions
Low WRN protein expression is associated with poor BCSS in patients with breast cancer. This can be used to optimize the risk stratification for personalized treatment.
Text
Werner Manuscript C Savva et al (1) (1)
- Proof
More information
Accepted/In Press date: 16 July 2020
e-pub ahead of print date: 25 July 2020
Keywords:
Biomarker, Breast Cancer, Helicase, WRN, Werner Syndrome Protein
Identifiers
Local EPrints ID: 444449
URI: http://eprints.soton.ac.uk/id/eprint/444449
ISSN: 1526-8209
PURE UUID: 2dc79b66-2507-4c59-a431-cf2c87d8155d
Catalogue record
Date deposited: 19 Oct 2020 16:34
Last modified: 17 Mar 2024 05:56
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Contributors
Author:
Maaz Sadiq
Author:
Omar Sheikh
Author:
Syed Karim
Author:
Sachin Trivedi
Author:
Andrew R. Green
Author:
Emad A. Rakha
Author:
Srinivasan Madhusudan
Author:
Arvind Arora
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