Dataset Information

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

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.

SUBMITTER: Kariri Y

PROVIDER: S-EPMC8960565 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Kariri Yousif Y Toss Michael S MS Alsaleem Mansour M Elsharawy Khloud A KA Joseph Chitra C Mongan Nigel P NP Green Andrew R AR Rakha Emad A EA

Breast cancer research and treatment 20220206 3

<h4>Background</h4>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).<h4>Methods</h4>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 ...[more]

PMID: 35124721

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Project description:The incidence of nasopharyngeal carcinoma (NPC) in Southeast Asia and Taiwan is high due to epidemiological factors. Cisplatin-based chemoradiotherapy is an important treatment strategy with excellent outcomes for patients with NPC. However, the outcomes for patients who are refractory to cisplatin-based therapy are poor. Methods for risk stratification of patients with NPC undergoing cisplatin-based chemoradiotherapy require to be investigated. A previous study indicated that ubiquitin-conjugating enzyme E2 B (UBE2B) was able to regulate alkylating drug sensitivity in NPC cells. In the present study, the clinical significance of UBE2B expression in patients with NPC was analyzed. Analysis of the two available NPC datasets containing the UBE2B expression profile (GSE12452 and GSE68799) was performed to evaluate the UBE2B expression levels in NPC tissues compared with nasopharyngeal mucosal epithelial tissues. Furthermore, immunohistochemical staining was performed using anti-UBE2B antibodies on samples from 124 patients with NPC who underwent cisplatin-based chemoradiotherapy. Disease-specific survival (DSS), distant metastatic-free survival (DMeFS) and local recurrence-free survival (LRFS) of patients with high and low UBE2B expression was analyzed. Furthermore, the associations between UBE2B expression and the biological behavior of NPC cells were investigated in vitro. Using public NPC datasets and in vitro studies, it was identified that UBE2B expression levels were increased in NPC tumor tissues compared with those in mucosal epithelial tissues. The cell proliferation ability was decreased in UBE2B-deficient NPC cells as compared with that in UBE2B-proficient cells. Immunohistochemical analysis of 124 NPC tissues from patients who underwent cisplatin-based chemoradiotherapy indicated that high UBE2B expression levels were associated with poor DSS, DMeFS and LRFS. Multivariate regression analysis of factors influencing survival also confirmed that high UBE2B expression levels were a statistically significant independent risk factor for poor clinical outcomes in terms of DSS [hazard ratio (HR), 1.955; 95% CI 1.164-3.282], DMeFS (HR, 2.141; 95% CI 1.206-3.801) and LRFS (HR, 2.557; 95 CI 1.313-4.981). In vitro analysis indicated that O6-methylguanine-DNA methyltransferase attenuated cisplatin sensitivity induced by knockdown of UBE2B in NPC cells. In conclusion, the present study demonstrated that high UBE2B expression is associated with poor clinical outcomes for patients with NPC treated with cisplatin-based chemoradiotherapy.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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