Ubc9 expression predicts chemoresistance in breast cancer

Abstract

Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in tumorigenesis. Whether Ubc9 is involved in the chemoresistance of breast cancer remains unknown. In this study, we aimed to evaluate the contribution of Ubc9 in the chemoresistance of breast cancer. Immunohistochemistry (IHC) was used to examine the expression level of Ubc9. Chi-square test, Wilcoxon test, and one-way ANOVA were applied to analyze the relationship between Ubc9 expression, clinicopathologic features, and clinical response to neoadjuvant chemotherapy. The significance of variables for survival was analyzed by the Cox proportional hazards model in a multivariate analysis. Kaplan-Meier survival curves were plotted and log-rank test was performed. The proportion of Ubc9-positive cells was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 ± 17.94)% vs. (5.82 ± 2.80)%, P < 0.001]. High Ubc9 expression was associated with poor differentiation (Χ² = 6.538, P = 0.038), larger tumor size (Χ² = 4.701, P = 0.030), advanced clinical stage (Χ² = 4.651, P = 0.031), lymph node metastasis (Χ² = 9.913, P = 0.010), basal-like phenotype (Χ² = 8.660, P = 0.034), and poor clinical response to neoadjuvant chemotherapy (Χ² = 11.09, P = 0.001). The expected 6-year cumulative disease-free survival rate was 87.32% in patients with low Ubc9 expression compared to 68.78% in those with high Ubc9 expression (Χ² = 4.289, P = 0.038). These data indicate that high Ubc9 expression correlates with poor response to chemotherapy and poor clinical prognosis.

Figure 1.. Expression of ubiquitin-conjugating enzyme 9 (Ubc9) protein in normal breast and invasive ductal breast carcinoma tissues (SP).

A, no expression of Ubc9 protein is seen in normal breast tissues. B, weak cytoplasmic and nuclear expression of Ubc9 protein in invasive ductal carcinoma tissues. Ubc9-positive cells are stained in brown. C, moderate cytoplasmic and nuclear expression of Ubc9 protein in invasive ductal carcinoma tissues. D, strong cytoplasmic and nuclear expression of Ubc9 protein in invasive ductal carcinoma tissues.

Figure 2.. The cumulative disease-free survival curves of patients with high or low Ubc9 expression.

The cumulative DFS rates were significantly higher in patients with low Ubc9 expression than in those with high Ubc9 expression (P < 0.05).