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

• Published in: Breast cancer research and treatment 2022-04, Vol.192 (3), p.529-539
• Main Authors: Kariri, Yousif, Toss, Michael S., Alsaleem, Mansour, Elsharawy, Khloud A., Joseph, Chitra, Mongan, Nigel P., Green, Andrew R., Rakha, Emad A.
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Apoptosis; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer research; Cell cycle; Cell migration; E-cadherin; Enzymes; ErbB-2 protein; Female; Gene expression; Genomes; Humans; Immunohistochemistry; Invasiveness; Matrix metalloproteinase; Medicine; Medicine & Public Health; N-Cadherin; Oncology; p53 Protein; Preclinical Study; Prognosis; Proteasomes; Protein expression; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Therapeutic targets; Tumors; Ubiquitin; Ubiquitin-conjugating enzyme; Ubiquitin-Conjugating Enzymes - genetics; Ubiquitin-Conjugating Enzymes - metabolism
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-022-06531-5

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.