Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer

Kariri, Yousif; Toss, Michael S.; Alsaleem, Mansour; Elsharawy, Khloud A.; Joseph, Chitra; Mongan, Nigel P.; Green, Andrew R.; Rakha, Emad A.

Abstract

Background
The Ubiquitin-conjugating enzyme 2C (UBE2C) is essential for the ubiquitin–proteasome system and is involved in cancer cell migration and apoptosis. This study aimed to determine the prognostic value of UBE2C in invasive breast cancer (BC).

Methods
UBE2C was evaluated using the Molecular Taxonomy of Breast Cancer International Consortium (n = 1980), The Cancer Genome Atlas (n = 854) and Kaplan–Meier Plotter (n = 3951) cohorts. UBE2C protein expression was assessed using immunohistochemistry in the BC cohort (n = 619). The correlation between UBE2C, clinicopathological parameters and patient outcome was assessed.

Results
High UBE2C mRNA and protein expressions were correlated with features of poor prognosis, including high tumour grade, large size, the presence of lymphovascular invasion, hormone receptor negativity and HER2 positivity. High UBE2C mRNA expression showed a negative association with E-cadherin, and a positive association with adhesion molecule N-cadherin, matrix metalloproteinases and cyclin-related genes. There was a positive correlation between high UBE2C protein expression and cell cycle-associated biomarkers, p53, Ki67, EGFR and PI3K. High UBE2C protein expression was an independent predictor of poor outcome (p = 0.011, HR = 1.45, 95% CI; 1.10–1.93).

Conclusion
This study indicates that UBE2C is an independent prognostic biomarker in BC. These results warrant further functional validation for UBE2C as a potential therapeutic target in BC.

Citation

Kariri, Y., Toss, M. S., Alsaleem, M., Elsharawy, K. A., Joseph, C., Mongan, N. P., …Rakha, E. A. (2022). Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer. Breast Cancer Research and Treatment, 192(3), 529-539. https://doi.org/10.1007/s10549-022-06531-5

• Journal Article Type: Article
• Acceptance Date: Jan 19, 2022
• Online Publication Date: Feb 6, 2022
• Publication Date: 2022-04
• Deposit Date: Jan 28, 2022
• Publicly Available Date: Feb 7, 2023
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 192
• Issue: 3
• Pages: 529-539
• DOI: https://doi.org/10.1007/s10549-022-06531-5
• Keywords: UBE2C; breast cancer; lymphovascular invasion; progression; prognosis; outcome
• Public URL: https://nottingham-repository.worktribe.com/output/7344687
• Publisher URL: https://link.springer.com/article/10.1007/s10549-022-06531-5
• Additional Information: This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://dx.doi.org/10.1007/s10549-022-06531-5