Abstract | INTRODUCTION: 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.
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Authors | Constantinos Savva, Maaz Sadiq, Omar Sheikh, Syed Karim, Sachin Trivedi, Andrew R Green, Emad A Rakha, Srinivasan Madhusudan, Arvind Arora |
Journal | Clinical breast cancer
(Clin Breast Cancer)
Vol. 21
Issue 1
Pg. 57-73.e7
(02 2021)
ISSN: 1938-0666 [Electronic] United States |
PMID | 32919863
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- WRN protein, human
- Werner Syndrome Helicase
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Topics |
- Aging, Premature
(metabolism)
- Breast Neoplasms
(complications, metabolism)
- Female
- Humans
- Werner Syndrome
(complications, metabolism)
- Werner Syndrome Helicase
(metabolism)
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