Abstract
BackgroundThe 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).MethodsUBE2C 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.ResultsHigh 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).ConclusionThis 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.
Highlights
Breast cancer (BC) is a heterogeneous disease comprising several biological subtypes and shows diverse behaviours and responses to therapy [1]
High Ubiquitin-conjugating enzyme 2C (UBE2C) mRNA expression was significantly associated with the presence of Lymphovascular invasion (LVI) (METABRIC cohort: p = 0.002, The Cancer Genome Atlas (TCGA) cohort: p < 0.001) and other factors characteristics of a poor prognosis, including larger tumour size (p < 0.001), high tumour grade (p < 0.001), ER and progesterone receptor (PR) negativity (p < 0.001) and human epidermal growth factor receptor 2 (HER2) positivity (p < 0.001; Table 1)
LVI is a serious consequence in breast cancer (BC) that contributes to cancer metastasis and shorter survival [8, 9]
Summary
Breast cancer (BC) is a heterogeneous disease comprising several biological subtypes and shows diverse behaviours and responses to therapy [1]. The UBE2C-encoded protein is involved in mitotic cyclin destructions and cell cycle progression; it potentially could participate in cancer development [4]. 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). 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. 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
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